Multi-centre, adaptive, randomized trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults - DisCoVeRy

• Register: EUCTR
• Last refreshed on: 6 April 2020
• Main ID: EUCTR2020-000936-23-FR
• Date of registration: 09/03/2020
• Prospective Registration: Yes
• Primary sponsor: INSERM
• Public title: Multi-centre, adaptive, randomized trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults - DisCoVeRy
• Scientific title: Multi-centre, adaptive, randomized trial of the safety and efficacy of treatments of COVID-19 in hospitalized adults - DisCoVeRy
• Date of first enrolment: 09/03/2020
• Target sample size: 3100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000936-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Luxembourg, Netherlands, Spain, United Kingdom

Contacts

• Name: Christelle DELMAS
• Affiliation: INSERM

• Name: Christelle DELMAS
• Affiliation: INSERM

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult =18 years of age at time of enrolment.
2. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to randomization.
3. Hospitalized patients with illness of any duration, and at least one of the following:
• Clinical assessment (evidence of rales/crackles on exam) AND SpO2 = 94% on room air,
OR
• Requiring supplemental oxygen, high flow oxygen devices, non invasive ventilation and/or mechanical ventilation
4. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. Acceptable birth control methods are listed in section 7.3.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1400

Exclusion criteria:
1. Refusal to participate expressed by patient or legally authorized representative if they are present
2. Liver enzymes ALT/AST > 5 times the upper limit of normal.
3. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30 mL/min)
4. Pregnancy or breast-feeding.
5. Anticipated transfer to another hospital, which is not a study site within 72 hours.
6. Patients treated with one of the antivirals evaluated in the study (i.e. remdesivir, interferon ß-1a, lopinavir/ritonavir, hydroxychloroquine) in the past 29 days
7. Contraindication to any study medication including allergy
8. Use of medications that are contraindicated with lopinavir/ritonavir i.e. drugs whose metabolism is highly dependent on the isoform CYP3A with narrow therapeutic range (e.g. amiodarone, colchicine, simvastatine)
9. Use of medications that are contraindicated with hydroxychloroquine: citalopram, escitalopram, hydroxyzine, domperidone, pipéraquine.
10. Human immunodeficiency virus infection under highly active antiretroviral therapy (HAART).
11. History of severe depression or attempted suicide or current suicidal ideation.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

COVID-19 - Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to randomization. - Illness of any duration, and at least one of the following: •Clinical assessment (evidence of rales/crackles on exam) AND SpO2 = 94% on room air, OR •Requiring mechanical ventilation and/or supplemental oxygen.

Intervention(s)

Trade Name: MYLAN
Product Name: lopinavir/ritonavir
Pharmaceutical Form:
INN or Proposed INN: LOPINAVIR
CAS Number: 192725-17-0
INN or Proposed INN: RITONAVIR
CAS Number: 155213-67-5

Trade Name: REBIF
Pharmaceutical Form:

Trade Name: Remdesivir
Pharmaceutical Form:

Trade Name: Plaquenil
Pharmaceutical Form: Tablet
INN or Proposed INN: HYDROXYCHLOROQUINE
CAS Number: 118-42-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: The overall objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19.
• The primary endpoint is subject clinical status (on a 7-point ordinal scale) at day 15

Secondary Objective: Evaluate clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by:

-Clinical Severity (Ordinal scale, National Early Warning Score (NEWS), Oxygenation, Mechanical Ventilation)
-Hospitalization : duration of hospitalization (days).
-Mortality
-Evaluate the safety of different investigational therapeutics through 28 days of follow-up as compared to the control arm
-Evaluate the virologic efficacy of different investigational therapeutics as compared to the control arm as assessed

Timepoint(s) of evaluation of this end point: Day 15

Primary end point(s): Clinical status of subject at day 15 (on a 7-point ordinal scale):
1. Not hospitalized, no limitations on activities
2. Not hospitalized, limitation on activities;
3. Hospitalized, not requiring supplemental oxygen;
4. Hospitalized, requiring supplemental oxygen;
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
6. Hospitalized, on invasive mechanical ventilation or ECMO;
7. Death.

Secondary Outcome(s)

Secondary end point(s): • Status on an ordinal scale assessed daily while hospitalized and on Days 15 and 29.
• NEWS assessed daily while hospitalized and on Days 15 and 29.
• Duration of supplemental oxygen (if applicable).
• Duration of mechanical ventilation (if applicable).
• Duration of hospitalization.
• In-hospital mortality, 28-day mortality and 90-day mortality with date and cause of death (if applicable).
• Grade 3 and 4 adverse events
• SAEs.
• White cell count, haemoglobin, platelets, creatinine, blood electrolytes (including kaliemia), prothrombin time and international normalized ratio (INR), glucose, total bilirubin, ALT, and AST on Days 1, 3, 5, 8, 11 (while hospitalized); and Days 15 and 29 (in the hospital, or, if discharged, at home or by returning to the hospital).

Timepoint(s) of evaluation of this end point: Day 15 and Day 29

Secondary ID(s)

C20-15

Ethics review

Status: Approved
Approval date: 06/03/2020
Contact: