Effects of Ginger on clinical manifestations and paraclinical features of patients with Severe Acute Respiratory Syndrome due to COVID-19: A structured summary of a study protocol for a randomized controlled trial

Abstract Objectives We investigate the effects of Ginger, compared to the usual therapeutic regimen on clinical manifestations and paraclinical features in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single center, randomized, double-blind, placebo-controlled clinical trial with parallel group design. Participants Inclusion criteria: 1. Patients admitted to Severe Acute Respiratory Syndrome (SARS) Departments at Shahid Mohammadi Hospital, Bandar Abbas, Iran 2. Age ≥18 years (weight ≥35 kg) 3. Hospitalized ≤48 hours 4. Confirmed SARS-CoV-2 diagnosis (Positive polymerase chain reaction (PCR)) 5. Moderate pneumonia and lung involvement in imaging 6. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm Exclusion criteria: 1. Underlying diseases, including heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders 2. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs 3. Severe and critical pneumonia 4. History of known allergy to Ginger 5. Pregnancy and breastfeeding Intervention and comparator Intervention group: The standard treatment regimen for COVID-19 along with Ginger-based herbal tablets (Vomigone ®, Dineh Pharmaceutical Company, Iran) at a dose of 1000 mg three times a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol, along with Vomigone-like placebo tablets (Dineh Pharmaceutical Company, Iran) at a dose of two tablets three times a day for a period of seven days. Main outcomes The primary outcome is recovery rate of clinical symptoms, including fever, dry cough, tiredness, and GI symptoms as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein within seven days of randomization. Time to improvement of clinical and paraclinical features along with the incidence of serious adverse events are the secondary outcomes within seven days of randomization. Randomization An interactive web-based system will be used to allocate eligible participants, based on the inclusion and exclusion criteria, to one of the two study arms (in a 1:1 ratio) using block randomization. Blinding (masking) All study participants, research coordinators, clinicians, nurses, and investigators will be blinded to the group assignment. Numbers to be randomized (sample size) A total of 84 participants will be randomized into two groups of 42 patients. Trial Status The protocol is Version 1.0, May 23, 2020. Recruitment began July 21, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N1”. Registration date is 23 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Effects of Licorice on clinical symptoms and laboratory signs in moderately ill patients with pneumonia from COVID-19: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04706-3 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Omid Safa ◽

Mehdi Hassani-Azad ◽

Mehdi Farashahinejad ◽

Parivash Davoodian ◽

Habib Dadvand ◽

...

Keyword(s):

Clinical Trial ◽

Standard Treatment ◽

Clinical Symptoms ◽

Intervention Group ◽

Control Group ◽

Root Extract ◽

Open Label ◽

Natural Medicine ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. Inclusion criteria: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. Intervention and comparator Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. Main outcomes The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. Randomization An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N2”, https://www.irct.ir/trial/47990. The registration date is 31 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05242-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Arash Rahimi ◽

Hamid Reza Samimagham ◽

Mehdi Hassani Azad ◽

Dariush Hooshyar ◽

Mohsen Arabi ◽

...

Keyword(s):

Clinical Trial ◽

Intensive Care Unit ◽

Intensive Care ◽

Pharmaceutical Company ◽

Study Protocol ◽

Intervention Group ◽

Phase Iii ◽

Arterial Oxygen ◽

Control Group ◽

Full Protocol

Abstract Objectives Severe acute respiratory infection (SARI) caused by the SARS-CoV-2 virus may cause lung failure and the need for mechanical ventilation. Infection with SARS-COV-2 can lead to activation of inflammatory factors, increased reactive oxygen species, and cell damage. In addition to mucolytic effects, N-Acetylcysteine has antioxidant effects that we believe can help patients recover. In this study, we evaluate the efficacy of N-Acetylcysteine in patients with severe COVID-19. Trial design This is a prospective, randomized, single-blinded, phase 3 controlled clinical trial with two arms (ratio 1:1) parallel-group design of 40 patients, using the placebo in the control group. Participants All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 ≤ saturation, arterial oxygen partial pressure ratio <300), pulmonary infiltration (> 50% of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive care unit of Shahid Mohammadi Hospital in Bandar Abbas and have positive PCR test results for SARS-Cov-2 and sign the written consent of the study will be included. Patients will be excluded from the study if they have a history of hypersensitivity to N-Acetylcysteine, pregnancy, or refuse to participate in the study. Intervention and comparator After randomization, participants in the intervention group receive standard of care (SOC) according to the National Committee of COVID-19 plus N-acetylcysteine (EXI-NACE 200mg/mL, in 10mL ampules of saline for parenteral injection (EXIR pharmaceutical company)) at a dose of 300 mg/kg equivalent to 20 gr as a slow single intravenous injection on the first day of hospitalization. In the control group patients receive SOC and placebo ( Sterile water for injection as the same dose). The placebo is identical in appearance to the N-acetylcysteine injection (EXIR pharmaceutical company as well). Main outcomes The primary endpoint for this study is a composite endpoint for the length of hospitalization in the intensive care unit and the patient's clinical condition. These outcomes were measured at the baseline (before the intervention) and on the 14th day after the intervention or on the discharge day. Randomisation Eligible participants (40) will be randomized in two arms in the ratio of 1: 1 (20 per arm) using online web-based tools and by permuted block randomization method. To ensure randomization concealment, random sequence codes are assigned to patients by the treatment team at the time of admission without knowing that each code is in the intervention or comparator group. Blinding (masking) All participants will be informed about participating in the study and the possible side effects of medication and placebo. Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. Numbers to be randomised (sample size) A total of 40 patients participate in this study, which are randomly divided; 20 patients in the intervention group will receive SOC and N-acetylcysteine, 20 patients in the control group will receive SOC and placebo. Trial status First version of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on February 14, 2021, with the local code 990573, and the recruitment started on March 2, 2021 and the expected recruitment end date is April 1, 2021. Trial registration The protocol was registered before starting participant recruitment entitled: Evaluation of the efficacy of N-Acetylcysteine in severe COVID-19 patients: a randomized controlled phase III clinical trial, IRCT20200509047364N3, at Iranian Registry of clinical trials on 20 February 2021. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

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Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04409-9 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 4

Author(s):

Pradeesh Sivapalan ◽

Charlotte Suppli Ulrik ◽

Rasmus Dahlin Bojesen ◽

Therese Sophie Lapperre ◽

Josefin Viktoria Eklöf ◽

...

Keyword(s):

Study Protocol ◽

Standard Treatment ◽

Controlled Trial ◽

Intervention Group ◽

Cardiac Conduction ◽

Control Group ◽

Qtc Interval ◽

Patient Will ◽

Full Protocol ◽

Fertile Women

Abstract Objectives The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. Trial design This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. Participants 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. Inclusion criteria: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. Intervention and comparator Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 Main outcomes • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") Randomisation The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). Blinding (masking) Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. Numbers to be randomised (sample size) This study requires 226 patients randomised 1:1 with 113 in each group. Trial Status Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). Trial registration ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

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The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04934-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Mahsa Miryan ◽

Davood Soleimani ◽

Leila Dehghani ◽

Karim Sohrabi ◽

Farzin Khorvash ◽

...

Keyword(s):

Clinical Trial ◽

Sample Size ◽

Clinical Symptoms ◽

Intervention Group ◽

Trial Registration ◽

Control Group ◽

Double Blind ◽

Double Blind Placebo ◽

Placebo Tablet ◽

Full Protocol

Abstract Objectives This study aims to assess the effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19). Trial design This is a Double-Blind, Placebo-Controlled, Parallel Arm, Randomized Phase ΙΙ Clinical Trial. Participants Patients with the confirmed COVID-19 based on the PCR test are eligible to participate in the trial if they are 18 to 75 years of age and have no history of the current use of warfarin or propolis supplement and presence of sensitivity to bee products. Patients will be recruited from the Al-Zahra hospital in Isfahan city, Isfahan, Iran. Intervention and comparator Participants (N=40) in the intervention group will receive an identical propolis tablet (containing 300 mg Iranian green propolis extract) three times a day for a period of 2 weeks. Participants (N=40) in the control group will receive an identical placebo tablet (containing 300 mg microcrystalline cellulose) three times a day for 2 weeks. All tablets are prepared by the Reyhan Naghsh Jahan Pharmaceutical Co., Isfahan, Iran. Main outcomes The main outcomes are changes in the coronavirus disease’s clinical symptoms including duration and severity from baseline to the end of 2 weeks. Randomization Eligible patients will be randomly allocated in a 1:1 ratio to the intervention or control group. Randomization will be performed on the basis of permuted block sizes of 4 and will be stratified according to sex categories. Randomization sequences will be prepared by the trial’s pharmacist with the use of random-number tables. Blinding (masking) The trial-group assignment will be concealed from all participants, clinicians, and investigators throughout the trial. To ensure blinding, randomization sequences will be kept in identical, opaque, sealed, sequentially numbered envelopes. Only the trial's pharmacist has access to the randomization list. Also, the placebo tablet will be similar to the propolis tablet in terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labelling, and packaging. Numbers to be randomized (sample size) The calculated total sample size is 80 patients, with 40 patients in each group. Trial status The protocol is Version 1.0, October 10, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by March 21, 2021. Trial registration The name of the trial register: The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial. IRCT registration number: IRCT20200802048267N1. Date of trial registration: 20 October 2020, retrospectively registered. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Preventive Efficacy of Tenofovir/Emtricitabine Against Severe Acute Respiratory Syndrome Coronavirus 2 Among Pre-Exposure Prophylaxis Users

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa455 ◽

2020 ◽

Vol 7 (11) ◽

Cited By ~ 1

Author(s):

Oskar Ayerdi ◽

Teresa Puerta ◽

Petunia Clavo ◽

Mar Vera ◽

Juan Ballesteros ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Clinical Manifestations ◽

Control Group ◽

Prevention Measures ◽

Duration Of Symptoms ◽

Chemiluminescent Microparticle Immunoassay ◽

Group 2 ◽

Tenofovir Alafenamide ◽

Sex With Men ◽

Exposure Prophylaxis

Abstract Background The preventive effect that tenofovir/emtricitabine (FTC) could have against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human immunodeficiency virus-negative people is unknown. The objective of this study was to analyze the seroprevalence and clinical manifestations of COVID-19 among users of pre-exposure prophylaxis (PrEP), disoproxil fumarate/FTC (TDF/FTC), or tenofovir alafenamide (TAF)/FTC and to compare it to that of a control group. Methods An observational descriptive study of the seroprevalence of antibodies for SARS-CoV-2 among men who have sex with men and transgender women without use of PrEP (Group 1; n = 250) and PrEP users with TDF/FTC (n = 409) or TAF/FTC (n = 91) (Group 2; n = 500) was conducted from May11, 2020 to June 27, 2020. All participants were provided with a structured questionnaire that collected information on the variables to be analyzed, and testing for immunoglobulin G antibodies to SARS-CoV-2 (chemiluminescent microparticle immunoassay) was then carried out. Results The seroprevalence of SARS-CoV-2 was 9.2% (95% confidence interval [CI], 5.9–13.5) in the group without PrEP and 15.0% (95% CI, 12.0–18.4) in the group with PrEP (P = .026). Among users of TDF/FTC it was 14.7% (95% CI, 11.4–18.5), and in users of TAF/FTC it was 16.5% (95% CI, 9.5–25.7) (P = .661). In those who tested positive for SARS-CoV-2 and receiving PrEP, 57.4% manifested symptoms, compared with 78.3% in the control group (P = .070). In users of TDF/FTC the figure was 53.3% and in users of TAF/FTC the figure was 73.3% (P = .100). The duration of symptoms was 11.5 days in the control group, 9.0 days in PrEP users (P = .116), 7.0 days in users of TDF/FTC, and 13.0 days in users of TAF/FTC (P = .100). Conclusions Users of PrEP, TDF/FTC, or TAF/FTC presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in relation to clinical manifestations. The PrEP users should use the same prevention measures as those indicated for the general population.

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A multi-center, randomized controlled trial by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-RCT) on the use of Kampo medicine, kakkonto with shosaikotokakikyosekko, in mild-to-moderate COVID-19 patients for symptomatic relief and prevention of severe stage: a structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04746-9 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Shin Takayama ◽

Takao Namiki ◽

Takashi Ito ◽

Ryutaro Arita ◽

Hajime Nakae ◽

...

Keyword(s):

Conventional Treatment ◽

Controlled Trial ◽

Kampo Medicine ◽

Control Group ◽

List Type ◽

Shortness Of Breath ◽

Exclusion Criteria ◽

Minimization Method ◽

Full Protocol

Abstract Objectives We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-to: KT) and shosaikotokakikyosekko (sho-saiko-to-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-to-moderate COVID-19 patients compared to those treated only with conventional treatment. Trial design The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-arm study. Participants Patients and inpatients will be recruited from 8 Japanese academic and non-academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Clinical stages of mild-to-moderate COVID-19 Symptomatic ≥ 20 years of age Male or female Ability to communicate in Japanese Outpatients and inpatients Provided informed consent Exclusion criteria: Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms Allergic to Kampo or Western medicines used in this study Pregnant and lactating Unable to follow up Participating in another clinical trial or interventional study Hypokalemic or taking oral furosemide or steroids Determined unsuitable for this study by the physician Intervention and comparator Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. Main outcomes The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. Randomization Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. Blinding (masking) Open-label with no blinding Numbers to be randomized (sample size) The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients’ symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). Trial status Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 Trial registration Japan Registry of Clinical Trials (jRCT) jRCTs021200020. Registered on August 25, 2020 Full protocol The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Evaluation of the effect of melatonin in patients with COVID-19-induced pneumonia admitted to the Intensive Care Unit: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05162-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ali Ameri ◽

Masoomeh Frouz Asadi ◽

Manoochehr Kamali ◽

Majid Vatankhah ◽

Ava Ziaei ◽

...

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Intensive Care ◽

Standard Treatment ◽

Clinical Symptoms ◽

Intervention Group ◽

Control Group ◽

Open Label ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). Trial design This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding Intervention and Comparator Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education’s protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education’s protocol for a period of seven days. Main outcomes The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. Randomization Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. Trial registration The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N7”. The registration date was February 16, 2021. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Efficacy and Safety of Ayurveda Intervention AYUSH 64 as add-on therapy for patients with COVID 19 infections: An open labelled, Parallel Group, Randomized controlled clinical trial

10.1101/2021.08.10.21261836 ◽

2021 ◽

Author(s):

Pankaj Bhardwaj ◽

Pawan Kumar Godatwar ◽

Jaykaran Charan ◽

Sanjeev Sharma ◽

Shazia Shafi ◽

...

Keyword(s):

Clinical Trial ◽

Sample Size ◽

Standard Treatment ◽

Control Group ◽

Controlled Clinical Trial ◽

Efficacy And Safety ◽

Randomized Controlled Clinical Trial ◽

Rt Pcr ◽

Randomized Controlled ◽

Parallel Group

COVID-19 pandemic impacted human health and the global economy. There is a huge uncertainty about the management of this disease, many drugs including some older drugs are being tested for efficacy and safety including the medicines from the complementary and alternative system. The Central Council for Research in Ayurvedic Sciences, India's apex body for Ayurvedic research and development under the Ministry of AYUSH, has developed a poly-herbal drug called AYUSH 64 for covid 19 which is considered to be having role in the COVID-19. This study was designed with the aim of assessing the efficacy and safety of AYUSH 64 in mild covid-19 patients as add on therapy with standard treatment. It was an open labelled, comparative, parallel group, Randomized controlled clinical trial. Total 60 stage I (mild) COVID 19 positive subjects were recruited, 30 were assigned to AYUSH 64 as an add on therapy along with the standard treatment and 30 were assigned to standard treatment as per the protocols. RT-PCR test was done as per government guidelines and protocol. Along with the RT-PCR clinical laboratory tests were also performed at screening as well as on the discharge as per the study schedule. Absolute events of negative RT-PCR at day 5 were more in the AYUSH 64 group as compared to control group but it was not statistically significant (70% Vs 54%, p=0.28). There was no significant difference between AYUSH 64 and control group for fever and respiratory symptoms or important lab parameters. No serious adverse event was reported from any group. AYUSH 64 has no significant beneficial effect as compared to control group, this may be because of the less sample size or no actual effect which need to be confirmed by studies with large sample size.

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Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04737-w ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Ava Ziaei ◽

Parivash Davoodian ◽

Habib Dadvand ◽

Omid Safa ◽

Soheil Hassanipour ◽

...

Keyword(s):

Clinical Symptoms ◽

Therapeutic Regimen ◽

Control Group ◽

Chronic Hypertension ◽

Trial Protocol ◽

Efficacy And Safety ◽

Positive Polymerase Chain Reaction ◽

Inflammatory Parameters ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. Trial design This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. Inclusion criteria: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. Intervention and comparator Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. Control group: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. Main outcomes The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1β (IL-1β), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. Randomization Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. Blinding (masking) All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. Numbers to be randomized (sample size) A total of 60 patients randomized into two groups (30 in each group). Trial Status The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. Trial registration The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N5”. The registration date was 14 August 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Efficacy of herbal medicine in the treatment and immunorehabilitation of preschool children with recurrent acute nasopharyngitis

Voprosy praktičeskoj pediatrii ◽

10.20953/1817-7646-2020-5-57-66 ◽

2020 ◽

Vol 15 (5) ◽

pp. 57-66

Author(s):

E.V. Shabaldina ◽

◽

D.R. Akhtyamov ◽

S.V. Grivtsova ◽

A.V. Shelkovnikov ◽

...

Keyword(s):

Herbal Medicine ◽

Standard Treatment ◽

Complete Blood Count ◽

Clinical Manifestations ◽

Posterior Wall ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Factor Α ◽

Necrosis Factor ◽

Pharyngeal Tonsil

Objective. To assess the efficacy of herbal medicine (HM) in the treatment and immunorehabilitation of children aged 2–6 years with recurrent acute nasopharyngitis. Patients and methods. This study included 327 children aged between 2 and 6 years; 85 of them were healthy and comprised the control group. The remaining children (n = 242) were divided into two groups by simple calendar randomization: the group receiving HM (n = 133) and the group receiving standard treatment (n = 109). All children have undergone the following examinations 45 days following treatment initiation: clinical examination, complete blood count, measurement of total IgE in peripheral blood, rhinocytogram, assessment of nasopharyngeal lavage and cells from the mucous membrane of the posterior wall of the oropharynx. Nasopharyngeal lavage was tested using enzyme-linked immunosorbent assay (ELISA) for the level of cytokines, including interleukins-1β and 4 (IL-1β, IL-4), interferons-α and -γ (IFNa, IFNy), and tumor necrosis factor-α (TNFα).DNA was isolated from the cells of the pharyngeal mucosa and pharyngeal tonsil and for subsequent analysis of the local biotope: bacteria, viruses, and fungi. Results. We found that HM helped to reduce clinical manifestations of acute nasopharyngitis, reduced local inflammation after treatment, and decreased the concentration of opportunistic flora, including Staphylococcus aureus. Conclusion. The inclusion of HM in the treatment regimen for children with recurrent nasopharyngitis increases treatment efficacy and prevents relapses. Key words: nasopharyngitis, immunorehabilitation

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