Antiviral Activity and Safety of Remdesivir in Bangladeshi Patients With Severe Coronavirus Disease (COVID-19)

Study Overview
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Brief Summary
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Background - A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in December 2019 as the cause of a respiratory illness COVID-19 in Wuhan City, China. WHO declared a public health emergency outbreak of this virus on 30 January 2020 and declared COVID-19 a global pandemic on 11 March, 2020. Bangladesh reported its first case on March 8, 2020 and first fatality on April 1, 2020. Bangladesh had shown a staggered course of COVID-19 transmission initially but a surge in cases was observed from April, 2020. Remdesivir remains as the only potential therapy for the treatment of COVID-19 till date. Based on several pre-clinical studies in SARS-CoV and MERS-CoV infections, Animal trials in COVID-19 and data from human trials, this randomized, controlled, open label trial will evaluate the antiviral activity and safety of Remdesivir in Bangladeshi hospitalized patients with severe COVID-19. This study finding will provide knowledge if Remdesivir is effective enough to treat Bangladeshi COVID-19 hospitalized patients with adequate safety and tolerability. The result of this study will help the key opinion leaders regarding the matter, to take appropriate decision regarding usage of Remdesivir for the treatment of COVID-19 in Bangladesh. Study Procedure - All patients will receive the standard medical care for COVID-19+ve at the respective hospitals. Vital signs will be recorded every 24 hrs for 1st 5 days then once in 2 days till discharge or as per the discretion of the attending physicians. After screening the COVID-19 confirmed patients will be randomized into 2 treatment arms. Patient's safety assessment e. g. blood parameters (CBC, Creatinine, SGPT, RBS, Creatinine, Creatinine Clearance) will be done on screening, day 5 and day 14 or discharge; Chest X-ray and ECG on screening and day 14 or discharge. SARS-CoV-2 (viral load) will be looked in on day 5, day 10 and day 14 or at the time of discharge. In case any study patient deteriorates during the study period will be managed as per the guideline of that particular hospital and if needed will be shifted to ICU. Patients who will recover will be discharged as per the national guideline for the COVID-19 hospitalized patients. Patients will be contacted at 28 days either over phone or in person to get their health status since discharge.

Official Title
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Antiviral Activity and Safety of Remdesivir in Bangladeshi Patients With Severe Coronavirus Disease (COVID-19): An Open Label, Multi-Center, Randomized Controlled Trial

Conditions
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Covid19

Intervention / Treatment
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* Drug: Remdesivir
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at time of signing Informed Consent Form Hospitalized with diagnosed COVID-19 confirmed by RT-PCR test ≤ 7 days before randomization with any one following criteria Respiratory distress (≥30 breaths/min); Finger oxygen saturation ≤93% at rest; Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤300mmHg Willingness of study participant to accept randomization to any assigned treatment arm Must agree not to enroll in another study of an investigational agent prior to completion of Day 28 of study Exclusion Criteria: Physician makes a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safely. Severe liver disease (Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal) Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration). Mechanically ventilated (including V-V ECMO) ≥ 5 days, or any duration of V-A ECMO. Known hypersensitivity to the Remdesivir, the metabolites, or formulation excipient Pregnancy or breast feeding. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remdesivir with Standard of Care Treatment for COVID-19 Infection<br>Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5. | Drug: Remdesivir<br>* Remdesivir INN 100 mg lyophilized powder for infusion<br>|
| Other: Standard of Care Treatment for COVID-19 Infection<br>Participants will receive continued standard of care therapy. | Other: Standard of Care<br>* Standard of Care Treatment for COVID-19 Infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospital stay (Days) |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Improvement (TTCI) | Time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. Six-category ordinal scale: Hospital discharge or meet discharge criteria Hospitalization, not requiring supplemental oxygen; Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); ICU/hospitalization, requiring NIV/ HFNC therapy; ICU, requiring ECMO and/or IMV; Death; | 28 Days | 
| All causes mortality |  | 28 Days | 
| Duration (days) of mechanical ventilation |  | 28 Days | 
| Duration (days) of supplemental oxygenation |  | 28 Days | 
| Time to 2019-nCoV RT-PCR negativity in Nasopharyngeal Swab |  | 28 Days | 
| Frequency of serious adverse drug events |  | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remdesivir