A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

JRCT ID: jRCT2031190264

Registered date:24/03/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Novel Coronavirus Infectious Disease (COVID-19)
• Date of first enrollment: 26/03/2020
• Target sample size: 100
• Countries of recruitment: USA,Japan,KOREA,Japan
• Study type: Interventional

Intervention(s)

Dosing and Administration
Subjects will be randomized 1:1 to receive either active product or placebo. Initially, the trial will have 2 arms:
-Remdesivir will be administered as a 200 mg IV loading dose on Day 1, followed by a 100 mg once-daily IV maintenance dose for the duration of the hospitalization up to a 10 day total course. If a subject is no longer hospitalized, then infusions will no longer be given.
-A matching placebo will be given at an equal volume at the same schedule.

Any dose that is delayed, but still the same study day, may be given. Any dose that is missed (not given that calendar day) is not made up.

Outcome(s)

Primary Outcome

The overall objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19.
-The primary objective will be determined by a pilot study of the first 100 subjects.
-Subject clinical status (8-point ordinal scale) at Day 15 is the default primary endpoint.

Secondary Outcome

1. Evaluate the clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by:
(1) Clinical Severity
1) Ordinal scale:
Time to an improvement of one category and two categories from Day 1 using an ordinal scale.
-Subject clinical status using ordinal scale at Days 3, 5, 8, 11, 22, and 29.
-Mean change in the ordinal scale from Day 1 to Days 3, 5, 8, 11, 15, 22, and 29.
2)National Early Warning Score (NEWS):
-Time to discharge or to a NEWS of <= 2 and maintained for 24 hours, whichever occurs first.
-Change from Day 1 to Days 3, 5, 8, 11, 15, and 29 in NEWS.
3)Oxygenation:
-Oxygenation free days to Day 29.
-Incidence and duration of new oxygen use during the study.
4)Non-invasive ventilation/high flow oxygen:
-Non-invasive ventilation/high flow oxygen - free days to Day 29.
-Incidence and duration of new non-invasive ventilation or high flow oxygen use during the study.
5)Invasive Mechanical Ventilation / extracorporeal membrane oxygenation (ECMO):
-Ventilator / ECMO free days to Day 29.
-Incidence and duration of new mechanical ventilation or ECMO use during the study.
(2) Hospitalization
1)Duration of hospitalization.
(3) Mortality
1)14-day mortality
2)28-day mortality

2. Evaluate the safety of different investigational therapeutics as compared to the control arm as assessed by:
(1) Cumulative incidence of SAEs through Day 29.
(2) Cumulative incidence of Grade 3 and 4 clinical and/or laboratory AEs through Day 29.
(3) Discontinuation or temporary suspension of infusions (for any reason)
(4) Changes in WBC with differential, hemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, AST, and PT over time (analysis of lab values in addition to AEs noted above).

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Admitted to a hospital with symptoms suggestive of COVID-19 infection.
2.Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
3.Understands and agrees to comply with planned study procedures.
4.Agrees to the collection of oropharyngeal (OP) swabs.
5.Male or non-pregnant female adult =>18 years of age at time of enrollment.
6.Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen collected < 72 hours prior to randomization.
Note - 72 hours is not necessarily time from initial diagnosis. If => 72 hours since positive PCR, the PCR may be repeated to assess eligibility.
7.Illness of any duration, and at least one of the following:
-Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
-Clinical assessment (evidence of rales/crackles on exam) AND SpO2 <= 94% on room air, OR
-Requiring supplemental oxygen, OR
-Requiring mechanical ventilation.
8.Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.
9.Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2.

Exclude criteria

1.ALT/AST > 5 times the upper limit of normal.
2.Estimated glomerular filtration rate (eGFR) < 50 or requiring dialysis.
3.Pregnancy or breast feeding.
4.Anticipated transfer to another hospital which is not a study site within 72 hours.
5.Allergy to any study medication.

Related Information

• Primary Sponsor: Ohmagari Norio
• Source(s) of Monetary Support: Ministry of Health, Labour and Welfare