Antiviral Agents Against COVID-19 Infection (REVOLUTIOn)
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ClinicalTrials.gov Identifier: NCT04468087 |
Recruitment Status :
Active, not recruiting
First Posted : July 13, 2020
Last Update Posted : February 28, 2022
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Condition or disease | Intervention/treatment | Phase |
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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 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 256 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 |
Actual Primary Completion Date : | August 4, 2021 |
Estimated Study Completion Date : | December 31, 2022 |

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

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.
Ages Eligible for Study: | 18 Years to 90 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
- Symptom duration <= 9 days
- SpO2 <= 94% in room air or need for supplemental oxygen to maintain SpO2> 94%
- 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:
- Patients in need of respiratory support with invasive mechanical ventilation;
- Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal;
- Total bilirubin > 2 mg/dL;
- Platelets <50,000 cel/L;
- Total neutrophil count <750 cell/L;
- 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;
- 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;
- 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;
- Pregnant or breast feeding patients;
- Known allergy or hypersensitivity to any study drug;
- 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;
- Patients currently using nucleoside or nucleotide analog drugs for any indication;
- Corrected Q interval T> 480 on the electrocardiogram;
- Heart rate <55 bpm;
- Patients in use or who recently used (<90 days) amiodarone;
- 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.

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
Brazil | |
Hospital do Coracao | |
Sao Paulo, SP, Brazil, 04005-000 |
Principal Investigator: | Israel S Maia, MSc | HCor Research Institute |
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: | February 28, 2022 |
Last Verified: | February 2022 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
covid-19 antivirals atazanavir daclatasvir |
sofosbuvir multiarm multistage study adaptive |
COVID-19 Infections Respiratory Tract Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases |
Respiratory Tract Diseases Atazanavir Sulfate HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |