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

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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Green tea intake and its effect on laboratory parameters and disease symptoms in hospitalised patients with Covid 19: a structured protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05462-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sara Mahmoodi ◽

Mojtaba Yousefi ◽

Omid Sadeghi ◽

Ali Mahmoodabadi ◽

Mohammadreza Sadriirani ◽

...

Keyword(s):

Green Tea ◽

Controlled Trial ◽

Intervention Group ◽

Total Sample ◽

Control Group ◽

List Type ◽

Disease Symptoms ◽

Laboratory Parameters ◽

Randomized Controlled ◽

Full Protocol

Abstract Objectives The current randomized controlled trial (RCT) will be conducted to assess the effect of green tea intake on disease symptoms and laboratory parameters including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count (CBC) in patients with mild-to-moderate Covid-19 infection. Trial design Randomized, double-blinded, parallel (1:1 ratio) clinical trial exploratory study Participants We will recruit patients with COVID-19 infection admitted to Yasuj Shahid Jalil Hospital in Yasuj City, Kohgiluyeh and Boyer-Ahmad Province, Iran. Participants’ inclusion criteria are as follows: Inclusion Criteria Patients aged ≥18 years COVID-19 diagnosis according to real-time polymerase chain reaction (RT-PCR) Exclusion Criteria Pregnancy or lactation Disseminated intravascular coagulation or any other types of coagulopathy Severe congestive kidney failure Having a history of participating in a clinical trial during the last 30 days Intervention and comparator Intervention: Two capsules containing 450 mg green tea extract along with routine treatment for COVID-19 patients in the intervention group. Two capsules containing placebo plus routine treatment for patients with COVID-19 infection. Capsules will be taken twice a day, after lunch and dinner, for 14 days. Main outcomes Changes in disease symptoms and laboratory parameters including CRP, ESR, and CBC after 14 days of the intervention compared to control group. Randomisation Eligible patients will be randomly assigned into the intervention or control group in a 1:1 ratio. Randomization will be performed based on 8 permuted blocks with block sizes of 10, and patients in the intervention and control groups will be matched according to sex and age categories. Randomization will be done using computer-generated random numbers (Randomization.com) Blinding (masking) The appearance of placebo and green tea capsules will be similar in terms of shape and color, and they will be packed in the same bags that will be prepared by the company. Also, the researcher and all participants will not be aware of the divisions until the end of the study. Numbers to be randomised (sample size) The total sample was determined based on CRP MCID in which high CRP levels were considered >2.6 mg/L. Accordingly, a total sample size of 37 patients for each intervention group was required. Trial Status The protocol is Version 1.0, on June 5, 2021. Recruitment will start on July 11, 2021, which is anticipated to be completed by September 21, 2021. Trial registration IRCT20150711023153N3 (https://www.irct.ir/trial/55948) retrospectively registered on June 4, 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 was eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Atorvastatin in Helicobacter Pylori Treatment: A Randomized Controlled Trial and Review

10.21203/rs.3.rs-575317/v1 ◽

2021 ◽

Author(s):

Mohammad Reza Mohammad Hoseini Azar ◽

Parham Porteghali ◽

Amin Sedokani

Keyword(s):

Helicobacter Pylori ◽

Standard Treatment ◽

Controlled Trial ◽

Intervention Group ◽

Trial Registration ◽

Control Group ◽

P Value ◽

Bismuth Subcitrate ◽

Significant Difference ◽

H Pylori

Abstract Background: Considering the increase in drug resistance over time to Helicobacter pylori treatment relying on the anti-inflammatory and antibacterial effects of atorvastatin to increase the success rate of H. pylori eradication, we examined the effect of adding atorvastatin to standard treatment of H. pylori eradication.Results: A total of 186 symptomatic patients who had been diagnosed with Helicobacter pylori infection and tested for H. pylori eradication were examined by a pathological response or positive urea breath test. Patients who received atorvastatin in addition to standard treatment were also identified based on a table of random numbers. Standard treatment included a 240mg bismuth subcitrate tablet, a 40mg pantoprazole tablet, a 500mg metronidazole tablet, and 2 capsules of 500mg amoxicillin, all taken BID for 14 days. After 4 weeks of treatment, all patients underwent stool testing for H. pylori fecal antigen. If the test was positive, the request was considered a failure of treatment, and if the test was negative, it was considered a successful eradication of H. pylori. The clinical trial registration code for this study is IRCT20190823044589N1. The eradication rate of H. pylori was 80% in the control group and 80.9% in the intervention group, which did not show a statistically significant difference between the two groups (P-value=0.971).Conclusion: Adding atorvastatin to 4-drug regimen of PPI, bismuth subcitrate, amoxicillin, and metronidazole as the first line of treatment for H. pylori eradication is ineffective.Trial registration: IRCT, IRCT20190823044589N1. Registered 28 December 2019 - Retrospectively registered, https://en.irct.ir/trial/41734

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The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04823-z ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

S. Natarajan ◽

C. Anbarasi ◽

P. Sathiyarajeswaran ◽

P. Manickam ◽

S. Geetha ◽

...

Keyword(s):

Data Analysis ◽

Vitamin C ◽

Sample Size ◽

Study Protocol ◽

Controlled Trial ◽

Severe Illness ◽

Control Group ◽

Rt Pcr ◽

Full Protocol ◽

Allocation Ratio

Abstract Objectives The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. Trial design A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. Participants Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. Intervention and comparator Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. Main outcomes The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. Randomisation The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. Blinding (masking) This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. Numbers to be randomised (sample size) Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. Trial status Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection Trial registration The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 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. 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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Evaluation of the efficacy and safety of favipiravir and interferon compared to lopinavir/ritonavir and interferon in moderately ill patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04747-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Mehdi Hassaniazad ◽

Ali Bazram ◽

Soheil Hassanipour ◽

Mohammad Fathalipour

Keyword(s):

Interferon Beta ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

List Type ◽

Peptic Ulcers ◽

Efficacy And Safety ◽

Open Label ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill. Trial design This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria: Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. Hospitalized ≤ 48 h. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. Exclusion criteria: Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. Severe and critical COVID-19 pneumonia. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. Pregnancy and breastfeeding. Intervention and comparator Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day. Control group: lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups. Main outcomes The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O2 saturation within 7 days of randomization. The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7 days of randomization. Randomization Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. 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 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group). Trial status The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020. Trial registration Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3. Registered on 22 July 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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Comparison of binocular game and patching in treating mild to moderate anisometropic amblyopia: a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05735-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Mohammad Etezad Razavi ◽

Marzieh Najjaran ◽

Jaber Mohseni ◽

Shokoufeh Aalaei

Keyword(s):

Clinical Trials ◽

Study Protocol ◽

Randomized Clinical Trials ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Medical Sciences ◽

Treatment Needs ◽

Parallel Group ◽

Research Designs

Abstract Background Amblyopia, as a neurodevelopmental preventable visual disorder, affects approximately 1.1 % in Asia. A binocular approach to treating amblyopia has been recently proposed. Whether the binocular playing game treatment is comparable to patching treatment needs further randomized clinical trials. To address this, the present research, designs, develops, and evaluates a new binocular game to treat amblyopia. Methods This study has been designed as a non-inferiority, randomized, two parallel-group, controlled trial. Forty-four patients between 4 and 12 years diagnosed with amblyopia will be randomly assigned to the control and intervention groups. In the intervention group, amblyopia treatment is provided with red-green anaglyphic glasses and a red filter placed in front of the amblyopic eye, along with a game to be played for 30 min twice a day. Those in the control group will receive patch therapy according to amblyopia treatment study protocol. The primary outcome is to change visual acuity in the amblyopic eye from the baseline to 3 months after randomization. Ethics and dissemination The Ethics Committee of Mashhad University of Medical sciences’ approval date was February 28, 2018, with a reference code of IR.MUMS.fm.REC.1396.783. Thus far, the recruitment of participants has not been completed and is scheduled to end in September 2021. The results will be disseminated in a peer-reviewed journal. Trial registration Iranian Registry of Clinical Trials IRCT20180217038768N1. Registered on 22 April 2019.

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The efficacy of the novel zinc-containing desensitizer CAREDYNE Shield on dentin hypersensitivity: a study protocol for a pilot randomized controlled trial

10.21203/rs.2.22474/v2 ◽

2020 ◽

Author(s):

Takashi Matsuura ◽

Megumi Mae ◽

Masayuki Ohira ◽

Yasunori Yamashita ◽

Ayako Nakazono ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Study Protocol ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

Dentin Hypersensitivity ◽

Root Caries ◽

The Novel ◽

Randomized Controlled ◽

Pilot Randomized Controlled Trial

Abstract Background: Dentin hypersensitivity (DH) is a condition characterized by short and sharp pain which will arise in response to tactile, chemical, thermal, evaporative or osmotic stimuli. The painful symptoms cause discomfort in patients and reduce their quality of life. Recently, the novel zinc-containing desensitizer CAREDYNE Shield has been developed as a new type of desensitizer that acts by inducing chemical occlusion of dentinal tubules, and releasing zinc ion for root caries prevention. However, the clinical effectiveness of CAREDYNE Shield on DH remains unclear. Therefore, the aim of this study is to evaluate the effectiveness of CAREDYNE Shield on DH by comparing with that of another desensitizer Nanoseal commonly used in Japan.Methods/Design: This study protocol is a two-arm parallel pilot randomized controlled trial. Forty DH patients will be randomly allocated to two groups. Participants in the intervention group will be treated with CAREDYNE Shield, while those in the control group will be treated with Nanoseal. The primary outcome is the reduction of pain intensity in response to air stimuli measured with a five-points verbal response scale from baseline to four weeks after the intervention, and Fisher's exact test will be used for analyses.Discussion: CAREDYNE Shield can be casually applied to subgingival areas and proximal surfaces because it reacts with only tooth substance. Furthermore, zinc has been reported to reduce the demineralization of enamel and dentin and inhibit biofilm formation, plaque growth and dentin collagen degradation. Therefore, CAREDYNE Shield may be expected to be a useful novel desensitizer that acts not only as a desensitizer but also as a root caries inhibitor.Trial registration:UMIN Clinical Trials Registry (UMIN-CTR), UMIN000038072. Registered on 21st September 2019.Trial statusThis study (protocol version number: version 1.4.0; approved on 22 October 2019) is ongoing. The recruitment of participants began in December 2019 and will be continued until November 2020 (1).

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Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04689-1 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 2

Author(s):

Nadir Kharma ◽

Stefan Roehrig ◽

Ahmed Atef Shible ◽

Moustafa Sayed Elshafei ◽

Dema Osman ◽

...

Keyword(s):

Mechanical Ventilation ◽

Sample Size ◽

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Intervention Group ◽

Sample Size Calculation ◽

Control Group ◽

Registration Number ◽

Full Protocol ◽

Allocation Ratio

Abstract Objectives To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. Trial design This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. Participants All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. Inclusion criteria: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. Exclusion criteria: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. Intervention and comparator The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. Main outcomes As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. Randomisation After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. Blinding (masking) Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. Numbers to be randomised (sample size) We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). Trial Status The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. Trial registration The protocol is registered before starting subject recruitment under the title: “Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial” in ClinicalTrials.org with the registration number: NCT04445935. Registered on 24 June 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). 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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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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Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial

Trials ◽

10.1186/s13063-021-05665-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jean-Christophe Richard ◽

Hodane Yonis ◽

Laurent Bitker ◽

Sylvain Roche ◽

Florent Wallet ◽

...

Keyword(s):

Mechanical Ventilation ◽

Tidal Volume ◽

Study Protocol ◽

Extracorporeal Circulation ◽

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Intervention Group ◽

Control Group ◽

Selective Reporting ◽

Link Type

Abstract Background Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34–50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg−1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. Methods The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg−1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg−1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. Discussion The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. Trial registration ClinicalTrials.govNCT04349618. Registered on April 16, 2020

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Combination treatment of autologous bone marrow stem cell transplantation and hyperbaric oxygen therapy for type 2 diabetes mellitus: A randomized controlled trial

Cell Transplantation ◽

10.1177/0963689719883813 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1632-1640

Author(s):

Esteban J. Estrada ◽

José Luis Decima ◽

Guillermo Bortman ◽

Javier Roberti ◽

Elida Beatriz Romero ◽

...

Keyword(s):

Standard Treatment ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

C Peptide ◽

Randomized Controlled ◽

Insulin Requirements ◽

One Year

The objective of this study was to compare standard treatment versus the combination of intrapancreatic autologous stem cell (ASC) infusion and hyperbaric oxygen treatment (HBOT) before and after ASC in the metabolic control of patients with type 2 diabetes mellitus (T2DM). This study was a prospective, randomized controlled trial. The combined intervention consisted of 10 sessions of HBOT before the intrapancreatic infusion of ASC and 10 sessions afterwards. ASCs were infused into the main arterial supply of the pancreas to maximize the presence of the stem cells where the therapeutic effect is most desired. A total of 23 patients were included (control group = 10, intervention group = 13). Age, gender, diabetes duration, number of medications taken, body weight and height, and insulin requirements were recorded at baseline and every three months. Also, body mass index, fasting plasma glucose, C-peptide, and HbA1c, C-peptide/glucose ratio (CPGR) were measured every three months for one year. HbA1c was significantly lower in the intervention group compared with control throughout follow-up. Overall, 77% of patients in the intervention group and 30% of patients in the control group demonstrated a decrease of HbA1c at 180 days (compared with baseline) of at least 1 unit. Glucose levels were significantly lower in the intervention group at all timepoints during follow-up. C-peptide levels were significantly higher in the intervention group during follow-up and at one year: 1.9 ± 1.0 ng/mL versus 0.7 ± 0.4 ng/mL in intervention versus control groups, respectively, p = 0.0021. CPGR was higher in the intervention group at all controls during follow-up. The requirement for insulin was significantly lower in the intervention group at 90, 180, 270, and 365 days. Combined therapy of intrapancreatic ASC infusion and HBOT showed increased metabolic control and reduced insulin requirements in patients with T2DM compared with standard treatment.

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