scholarly journals Role of Interferon Therapy in Severe COVID-19: The COVIFERON Randomized Controlled Trial

2021 ◽  
Author(s):  
Ilad Alavi Darazam ◽  
Mohamad Amin Pourhoseingholi ◽  
Shervin Shokouhi ◽  
Seyed Sina Naghibi Irvani ◽  
Majid Mokhtari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Controlled Trial ◽  
Ordinal Scale ◽  
Control Group ◽  
P Value ◽  
Open Label ◽  
Subcutaneous Injections ◽  
Positive Effects ◽  
Significant Difference ◽  
Registration Number

Abstract Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI=1.10-5.17, P-value=0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI=0•63-3•16, P-value=0•395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies. Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768)

scholarly journals Role of interferon therapy in severe COVID-19: the COVIFERON randomized controlled trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ilad Alavi Darazam ◽  
Shervin Shokouhi ◽  
Mohamad Amin Pourhoseingholi ◽  
Seyed Sina Naghibi Irvani ◽  
Majid Mokhtari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Controlled Trial ◽  
Ordinal Scale ◽  
Control Group ◽  
P Value ◽  
Open Label ◽  
Subcutaneous Injections ◽  
Positive Effects ◽  
Significant Difference ◽  
Registration Number

AbstractType 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10–5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63–3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies.Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

scholarly journals Safety and Effectiveness of High-Dose Vitamin C in Patients with COVID-19; A Randomized Controlled open-label Clinical Trial ‎

2021 ◽  
Author(s):  
Saeidreza JamaliMoghadamSiahkali ◽  
Besharat Zarezade ◽  
Sogol Koolaji ◽  
Seyed Ahmad Seyed Alinaghi ◽  
Abolfazl Zendehdel ◽  
...  
Keyword(s):  
Vitamin C ◽  
Controlled Trial ◽  
Control Treatment ◽  
Control Group ◽  
P Value ◽  
Case Group ◽  
High Dose ◽  
Open Label ◽  
Significant Difference ◽  
High Dose Vitamin

Abstract Background: To assess the effectiveness of vitamin C treatment against coronavirus disease 2019 (COVID-19)Methods: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received high-dose of vitamin C (six gr daily) added to the same regimen. Results: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. On the 3rd day of hospitalization, the mean core body temperatures was significantly lower and SpO2 was higher In the case group (p value = 0.001, and 0.014, respectively). The median length of hospitalization in case group which was significantly longer than the control group (8.5 days vs. 6.5 days) (p value = 0.0280). There was no significant difference in SpO2 levels at discharge time, the length of ICU stay, and mortality between the two groups.Conclusions: We did not find significantly better outcomes in the group who were treated with high-dose vitamin C in addition to the main treatment regimen at discharge.Trial registration: The project was registered by Iranian Registry of Clinical Trials.IRCT20200411047025N1

scholarly journals Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keivan Ranjbar ◽  
Mohsen Moghadami ◽  
Alireza Mirahmadizadeh ◽  
Mohammad Javad Fallahi ◽  
Vahid Khaloo ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Clinical Status ◽  
Intervention Group ◽  
Length Of Hospital Stay ◽  
Ordinal Scale ◽  
Control Group ◽  
Randomized Controlled ◽  
Group Data ◽  
Significant Difference

Abstract Background Although almost a year has passed since the Coronavirus disease 2019 (COVID-19) outbreak and promising reports of vaccines have been presented, we still have a long way until these measures are available for all. Furthermore, the most appropriate corticosteroid and dose in the treatment of COVID-19 have remained uncertain. We conducted a study to assess the effectiveness of methylprednisolone treatment versus dexamethasone for hospitalized COVID-19 patients. Methods In this prospective triple-blinded randomized controlled trial, we enrolled 86 hospitalized COVID-19 patients from August to November 2020, in Shiraz, Iran. The patients were randomly allocated into two groups to receive either methylprednisolone (2 mg/kg/day; intervention group) or dexamethasone (6 mg/kg/day; control group). Data were assessed based on a 9-point WHO ordinal scale extending from uninfected (point 0) to death (point 8). Results There were no significant differences between the groups on admission. However, the intervention group demonstrated significantly better clinical status compared to the control group at day 5 (4.02 vs. 5.21, p = 0.002) and day 10 (2.90 vs. 4.71, p = 0.001) of admission. There was also a significant difference in the overall mean score between the intervention group and the control group, (3.909 vs. 4.873 respectively, p = 0.004). The mean length of hospital stay was 7.43 ± 3.64 and 10.52 ± 5.47 days in the intervention and control groups, respectively (p = 0.015). The need for a ventilator was significantly lower in the intervention group than in the control group (18.2% vs 38.1% p = 0.040). Conclusion In hospitalized hypoxic COVID-19 patients, methylprednisolone demonstrated better results compared to dexamethasone. Trial registration The trial was registered with IRCT.IR (08/04/2020-No. IRCT20200204046369N1).

Effectiveness of sustained natural apophyseal glides in females with cervicogenic headache: A randomized controlled trial

2021 ◽  
pp. 1-7
Author(s):  
Muhammad Kashif ◽  
Nosheen Manzoor ◽  
Rimsha Safdar ◽  
Hafsa Khan ◽  
Maryam Farooq ◽  
...  
Keyword(s):  
Treatment Group ◽  
Controlled Trial ◽  
Neck Disability Index ◽  
Placebo Treatment ◽  
Cervicogenic Headache ◽  
Control Group ◽  
P Value ◽  
Head Positioning ◽  
Significant Difference ◽  
Neck Disability

BACKGROUND: Cervicogenic headache (CGH) is a common condition that results in significant disability. To treat this dysfunction, Mulligan described sustained natural apophyseal gliders (SNAGs) as a manual therapy approach. However, only inconclusive short-term evidence exists for treating CGH with SNAGs. OBJECTIVE: The present study aims to investigate the effect of SNAGs in the treatment of CGH. METHODS: Fourty female patients ranging from 20 to 40 years with CGH were randomly assigned to two groups: 20 in a treatment group and 20 in a control group. SNAGs were applied to the treatment group while the control group received placebo treatment. Both groups received their respective treatment for 20 minutes, alternately three times per week, for a total of 12 times in four weeks. The outcome measures were the Neck Disability Index (NDI) and the Visual Analogue Scale (VAS). Participants were assessed at baseline and at the end of each week. The data was analyzed using SPSS version 20. Independent t-testing was used to reveal changes between groups. One-way ANOVA was used to determine changes within groups. The level of significance was P< 0.05. RESULTS: Twenty participants (100%) in the treatment group and 17 (85%) in the control group had a history of headache aggravation with active movements or passive head positioning. There was no significant difference at baseline (p> 0.05), indicating that both groups were homogeneous at the time of recruitment. The p value (p< 0.05) showed a significant difference in pain and level of disability at three and four weeks (p< 0.05) in patients treated with SNAGs. However, the cervical range of motion (ROM) showed a statistically significant improvement in flexion and extension in the treatment group (p< 0.05) while there was no significant improvement in side flexion and rotation ROM in both groups (p> 0.05). CONCLUSION: This study found that SNAGs were effective in reducing pain and neck disability and improved ROM in females with CGH.

scholarly journals Effect of conversion from calcineurin inhibitors to everolimus on hepatitis C viremia in adult kidney transplant recipients

2018 ◽  
Vol 40 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Larissa Sgaria Pacheco ◽  
Valter Duro Garcia ◽  
Ronivan Luis Dal Prá ◽  
Bruna Doleys Cardoso ◽  
Mariana Ferras Rodrigues ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Controlled Trial ◽  
Calcineurin Inhibitors ◽  
Control Group ◽  
P Value ◽  
Kidney Transplant Recipients ◽  
Positive Serology ◽  
Open Label ◽  
Adult Kidney ◽  
Group 1

ABSTRACT Introduction: Currently, there is no specific immunosuppressive protocol for hepatitis C (HCV)-positive renal transplants recipients. Thus, the aim of this study was to evaluate the conversion effect to everolimus (EVR) on HCV in adult kidney recipients. Method: This is an exploratory single-center, prospective, randomized, open label controlled trial with renal allograft recipients with HCV-positive serology. Participants were randomized for conversion to EVR or maintenance of calcineurin inhibitors. Results: Thirty patients were randomized and 28 were followed-up for 12 months (conversion group, Group 1 =15 and control group, Group 2 =13). RT-PCR HCV levels reported in log values were comparable in both groups and among patients in the same group. The statistical analysis showed no interaction effect between time and group (p value G*M= 0.852), overtime intra-groups (p-value M=0.889) and between group (p-value G=0.286). Group 1 showed a higher incidence of dyslipidemia (p=0.03) and proteinuria events (p=0.01), while no difference was observed in the incidence of anemia (p=0.17), new onset of post-transplant diabetes mellitus (p=1.00) or urinary tract infection (p=0.60). The mean eGFR was similar in both groups. Conclusion: Our study did not show viral load decrease after conversion to EVR with maintenance of antiproliferative therapy.

scholarly journals Protocol for the DisCoVeRy trial: multicentre, adaptive, randomised trial of the safety and efficacy of treatments for COVID-19 in hospitalised adults

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e041437
Author(s):  
Florence Ader
Keyword(s):  
Controlled Trial ◽  
Clinical Status ◽  
Antiviral Agents ◽  
Randomised Trial ◽  
Phase Iii ◽  
Ordinal Scale ◽  
Control Group ◽  
National Agency ◽  
Open Label ◽  
Hospitalised Patients

IntroductionTo find effective and safe treatments for COVID-19, the WHO recommended to systemically evaluate experimental therapeutics in collaborative randomised clinical trials. As COVID-19 was spreading in Europe, the French national institute for Health and Medical Research (Inserm) established a transdisciplinary team to develop a multi-arm randomised controlled trial named DisCoVeRy. The objective of the trial is to evaluate the clinical efficacy and safety of different investigational re-purposed therapeutics relative to Standard of Care (SoC) in patients hospitalised with COVID-19.Methods and analysisDisCoVeRy is a phase III, open-label, adaptive, controlled, multicentre clinical trial in which hospitalised patients with COVID-19 in need of oxygen therapy are randomised between five arms: (1) a control group managed with SoC and four therapeutic arms with re-purposed antiviral agents: (2) remdesivir + SoC, (3) lopinavir/ritonavir + SoC, (4) lopinavir/ritonavir associated with interferon (IFN)-β−1a + SoC and (5) hydroxychloroquine + SoC. The primary endpoint is the clinical status at Day 15 on the 7-point ordinal scale of the WHO Master Protocol (V.3.0, 3 March 2020). This trial involves patients hospitalised in conventional departments or intensive care units both from academic or non-academic hospitals throughout Europe. A sample size of 3100 patients (620 patients per arm) is targeted. This trial has begun on 22 March 2020. Since 5 April 2020, DisCoVeRy has been an add-on trial of the Solidarity consortium of trials conducted by the WHO in Europe and worldwide. On 8 June 2020, 754 patients have been included.Ethics and disseminationInserm is the sponsor of DisCoVeRy. Ethical approval has been obtained from the institutional review board on 13 March 2020 (20.03.06.51744) and from the French National Agency for Medicines and Health Products (ANSM) on 9 March 2020. Results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04315948 Eudra-CT 2020-000936-23.

scholarly journals SARS-CoV-2 organising pneumonia: ‘Has there been a widespread failure to identify and treat this prevalent condition in COVID-19?’

2020 ◽  
Vol 7 (1) ◽  
pp. e000724 ◽  
Author(s):  
Pierre Kory ◽  
Jeffrey P Kanne
Keyword(s):  
Viral Infections ◽  
Controlled Trial ◽  
Ventilatory Support ◽  
Treatment Strategies ◽  
Pulmonary Involvement ◽  
Control Group ◽  
Positive Effects ◽  
Histological Variant ◽  
Lung Biopsies ◽  
Randomised Controlled

Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of ‘silent hypoxemia’, ‘happy hypoxemics’ and ‘atypical ARDS’, all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with ‘pulse’ doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.

scholarly journals Perioperative rifaximin is not associated with enhanced functional and volumetric recovery after major liver resection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jan Bednarsch ◽  
Zoltan Czigany ◽  
Sven H. Loosen ◽  
Lara Heij ◽  
Lorenz Ruckgaber ◽  
...  
Keyword(s):  
Liver Function ◽  
Primary Endpoint ◽  
Major Hepatectomy ◽  
Controlled Trial ◽  
Liver Volume ◽  
Relative Increase ◽  
Control Group ◽  
Open Label ◽  
Significant Difference ◽  
The Impact

AbstractThe objective of this randomized controlled trial (RCT) was to assess the impact of rifaximin on the course of liver function, liver regeneration and volumetric recovery in patients undergoing major hepatectomy. The ARROW trial was an investigator initiated, single-center, open-label, phase 3 RCT with two parallel treatment groups, conducted at our hepatobiliary center from 03/2016 to 07/2020. Patients undergoing major hepatectomy were eligible and randomly assigned 1:1 to receive oral rifaximin (550 mg twice daily for 7–10 or 14–21 days in case of portal vein embolization preoperatively and 7 days postoperatively) versus no intervention. Primary endpoint was the relative increase in postoperative liver function measured by LiMAx from postoperative day (POD) 4 to 7. Secondary endpoint were the course of liver function and liver volume during the study period as well as postoperative morbidity and mortality. Between 2016 and 2020, 45 patients were randomized and 35 patients (16 individuals in the rifaximin and 19 individuals in the control group) were eligible for per-protocol analysis. The study was prematurely terminated following interim analysis, due to the unlikelihood of reaching a significant primary endpoint. The median relative increase in liver function from POD 4 to POD 7 was 27% in the rifaximin group and 41% in the control group (p = 0.399). Further, no significant difference was found in terms of any other endpoints of functional liver- and volume regeneration or perioperative surgical complications following the application of rifaximin versus no intervention. Perioperative application of rifaximin has no effect on functional or volumetric regeneration after major hepatectomy (NCT02555293; EudraCT 2013-004644-28).

scholarly journals Effects of Bupropion on Cognitive Function in Schizophrenia: A Double Blind Randomized Controlled Trial

2016 ◽  
Vol 9 (5) ◽  
pp. 67
Author(s):  
Mansoureh Mirzadeh ◽  
Najmeh Shahini ◽  
Masoud Kashani Lotf Abadi ◽  
Maryam Tavakoli ◽  
Arash Javanbakht ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Cognitive Function ◽  
Rating Scale ◽  
Controlled Trial ◽  
Control Group ◽  
P Value ◽  
Double Blind ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Schizophrenic Patients

<p>Smoking habits are common in schizophrenic patients. Nicotine can suppress negative symptoms and cognitive impairments. The aim of this study was to determine the efficacy of bupropion on cognitive function in schizophrenic patients.<strong> </strong>This study is a double blind randomized controlled trial in a large referral psychiatric university hospital in Iran. Ninety smoker schizophrenic patients were randomly allocated (based on DSM -IV TR criteria) in two groups (46 patients for case group and 44 patients in control group). They get risperidone up to 6 mg/d and bupropion up to 400 mg/d .clinical assessment (Positive and Negative Syndrome Scale (PANSS), Brief psychiatric rating scale (BPRS) were taken in beginning of study, 14<sup>th</sup> and 28<sup>th</sup> days of study. Cognitive assessment (Stroop, Digit Span, and Wechsler, Wisconsin) were taken in begging of study, the days 2<sup>nd</sup>, 7<sup>th</sup>, 14<sup>th</sup>, 28<sup>th</sup>. All data were analyzed by SPSS Ver. 17 with analytic and descriptive tests. Mean age of patients was 37.66±1.01. Mean duration of disorder was 11.63±.98 years. The scores were significantly lower at the day 28<sup>th</sup> compared to the beginning of the study in both groups in Wechsler, Stroop color word , Stroop word , Stroop color , BPRS, PANSS p value ≤0.05 .The difference between the two treatments was not significant as indicated by the effect of group, the between-subjects factor<strong> </strong><strong>p </strong>value ≥0.05. In this study, the side effects were examined and there was no significant difference between the two groups p value ≥0.05.<strong> </strong>Augmentation of bupropion to routine treatment improves cognitive symptoms of schizophrenia in abstinence of tobacco.</p>

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

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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