Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antiviral Agents Against COVID-19 Infection (REVOLUTIOn)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04468087
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : May 28, 2021
Sponsor:
Information provided by (Responsible Party):
Hospital do Coracao

Brief Summary:
A key strategy in the treatment of COVID-19 would be to find an effective antiviral agent that would decrease the peak viral load and, consequently, the associated degree of immunopathological damage that follows this phase. The clinically approved substances considered for this study are used for treatment of other virus diseases, like HIV (atazanavir) and HCV (sofosbuvir and daclatasvir). Severe progression of COVID-19 among patients under treatment for these aforementioned viruses is empirical less common. Besides, the clinical rationale, there are pre-clinical evidence pointing out that patients with COVID-19 could benefit from treatments with atazanavir, sofosbuvir and daclatasvir.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Atazanavir Drug: Daclatasvir 60 mg Drug: Sofusbuvir + Daclastavir 60 mg Drug: Placebo Atazanavir Drug: Placebo Daclatasvir 60 mg Drug: Placebo Sofusbuvir + Daclatasvir 60 mg Phase 2 Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1005 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, multicenter, multi-arm, multi-stage, study. Adults, COVID-19 confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) or SARS-Cov2 Antigen hospitalized patients with ≤ 9 days duration of symptoms and SpO2<=94% will be randomly assigned to receive antivirals with potential effectiveness for SARS-CoV-2.

The study is planned to be an adaptive phase II / III study. The phase II will be divided into 2 stages: first and second stages. First stage will allocate patients into a 3:3:3:1:1:1 allocation ratio (5 for each treatment group and 1 for placebo) and second stage will allocate into 2:2:1:1 (2 for each treatment group and 1 for placebo). The phase 3 study will then proceed in a 2:1 allocation (2 treatments for each placebo).

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double-blind study for participants of the same active drug and researchers. Both participant and investigator can know, after randomization, which medication they were allocated to. However, none will know whether the capsule to be administered is active or placebo, ensuring blinding within that specific group to which the participant was allocated.
Primary Purpose: Treatment
Official Title: Antiviral for Adult Patients Hospitalized for SARS-CoV-2 Infection: a Randomized, Phase 2/3, Multicenter, Placebo Controlled, Adaptive, Multi-arm, Multi-stage Clinical Trial - Coalition Brazil COVID-19 IX: REVOLUTIOn
Actual Study Start Date : February 15, 2021
Estimated Primary Completion Date : July 28, 2021
Estimated Study Completion Date : July 30, 2021

Arm Intervention/treatment
Experimental: Atazanavir
600 mg (2 capsules) twice daily on the first day and 300 mg (1 capsule) twice daily for the subsequent 9 days.
Drug: Atazanavir
600 mg (2 capsules) twice daily on the first day and 300 mg (1 capsule) twice daily for the subsequent 9 days.
Other Name: Active Group

Experimental: Daclatasvir 60 mg
initial dose of 120mg (2 capsules), followed by 60mg (1 capsule) once daily for 9 days.
Drug: Daclatasvir 60 mg
initial dose of 120mg (2 capsules), followed by 60mg (1 capsule) once daily for 9 days.
Other Name: Active Group

Experimental: Sofusbuvir + Daclatasvir 60 mg
400 mg twice daily (2 capsules) on the first day and 400 mg (1 capsules) once daily for the subsequent 9 days (sofosbuvir) + initial dose of 120mg (2 capsules), followed by 60mg (1 capsule) once a day for 9 days (daclastavir)
Drug: Sofusbuvir + Daclastavir 60 mg
400 mg twice daily (2 capsules) on the first day and 400 mg (1 capsules) once daily for the subsequent 9 days (sofusbuvir) + initial dose of 120mg (2 capsules), followed by 60mg (1 capsule) once a day for 9 days (daclastavir)
Other Name: Active Group

Drug: Placebo Sofusbuvir + Daclatasvir 60 mg
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Other Name: Placebo group

Placebo Comparator: Placebo Atazanavir
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Drug: Placebo Atazanavir
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Other Name: Placebo group

Placebo Comparator: Placebo Daclatasvir
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Drug: Placebo Daclatasvir 60 mg
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Other Name: Placebo group

Placebo Comparator: Placebo Sofusbuvir + Daclatasvir
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Drug: Placebo Sofusbuvir + Daclatasvir 60 mg
2 capsules twice daily on the first day and 1 capsule twice daily for the subsequent 9 days.
Other Name: Placebo group




Primary Outcome Measures :
  1. Phase II first step: Change in the slope of SARS-COV 2 viral load [ Time Frame: days 3, 6 and 10 after randomization ]
    Change in the slope of the SARS-COV 2 log viral load evaluated by nasopharyngeal swab samples assessed at baseline and days 3, 6 and 10 after randomization (isolated antiviral).

  2. Phase II second step: Change in the slope of SARS-COV 2 viral load [ Time Frame: days 3, 6 and 10 after randomization ]
    Change in the slope of the SARS-COV 2 log viral load curve evaluated by nasopharyngeal swab samples assessed at baseline and days 3, 6 and 10 after randomization (combined antiviral).

  3. Phase III: Number of free days from respiratory support [ Time Frame: 15 days ]
    Number of days without oxygen, non-invasive ventilation/high flow nasal cannula or need for mechanical ventilation in 15 days.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults (≥ 18 years) hospitalized with COVID-19:

    • SARS-CoV-2 positive RT-PCR or Antigen test
    • Typical clinical history and chest CT with typical findings, pending RT-PCR for SARS-CoV-2
  2. Symptom duration <= 9 days
  3. SpO2 <= 94% in room air or need for supplemental oxygen to maintain SpO2> 94%
  4. The patient consents to participate in the study and is willing to comply with all study procedures, including the collection of virology samples

Exclusion Criteria:

  1. Patients in need of respiratory support with CNAF, NIV or invasive mechanical ventilation;
  2. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal;
  3. Total bilirubin > 2 mg/dL;
  4. Platelets <50,000 cel/L;
  5. Total neutrophil count <750 cell/L;
  6. Renal dysfunction (estimated glomerular filtration rate [eGFR] <30 mL / min / 1.73 m2, using the MDRD or CKD-EPI method); and pre-defined renal failure stage 3 according to AKINx classification with serum creatinine> 4 mg / dl or patient already on renal replacement therapy;
  7. Previously known liver disease (liver cirrhosis), defined as a report by the participant or written in the respective cirrhosis chart, esophageal varices, or the presence of clinical ascites on examination;
  8. Decompensated congestive heart failure defined as the presence of dyspnea, edema of the lower limbs or rales on pulmonary auscultation, jugular turgency or chest X-ray with signs of pulmonary congestion;
  9. Pregnant or lactating patients;
  10. Known allergy or hypersensitivity to any study drug;
  11. Hepatitis C carrier (HCV RNA positive), active Hepatitis B (positive surface antigen in the past), or HIV (ELISA and confirmatory Western Blot in the past). New screening tests are NOT required;
  12. Patients currently using nucleoside or nucleotide analog drugs for any indication;
  13. Corrected Q interval T> 480 on the electrocardiogram;
  14. Heart rate <55 bpm;
  15. Patients in use or who recently used (<90 days) amiodarone;
  16. Women of childbearing potential and men with a partner of childbearing potential who do NOT agree to use two contraceptive methods (including barrier method) for 100 days.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04468087


Contacts
Layout table for location contacts
Contact: Israel Maia, MSc 11 +55113053 6611 ext 8206 ismaia@hcor.com.br

Locations
Layout table for location information
Brazil
Hospital do Coracao Recruiting
Sao Paulo, SP, Brazil, 04005-000
Contact: Alexandre B Cavalcanti, MD, PhD    +55 11 30536611 ext 8102    abiasi@hcor.com.br   
Sponsors and Collaborators
Hospital do Coracao
Investigators
Layout table for investigator information
Principal Investigator: Israel S Maia, MSc HCor Research Institute
Layout table for additonal information
Responsible Party: Hospital do Coracao
ClinicalTrials.gov Identifier: NCT04468087    
Other Study ID Numbers: REVOLUTIOn
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: May 28, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital do Coracao:
covid-19
antivirals
atazanavir
daclatasvir
sofosbuvir
multiarm multistage study
adaptive
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Atazanavir Sulfate
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents