A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)

NCT04504032 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: Gates MRI - COD-01-T01-012020-005395-35
• Study Type: interventional
• Target: 497
• Locations: 2 countries
• Sites: 20

Brief Summary

The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.

Conditions

COVID-19

Keywords

Rivaroxaban; Xarelto; Coronavirus; COVID-19; Coronavirus disease 2019

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35

  An AE is any untoward medical occurrence that occurs in a participant. An AE can be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with treatment, whether considered related to the product. AEs may include the onset of a new illness or undesirable medical condition or the exacerbation of pre-existing medical conditions. AE severity was graded as Grade 3 (Severe) and Grade 4 (Potentially Life-threatening) per the specific toxicity grading by the Division of Acquired Immunodeficiency Syndrome (DAIDS) AE Grading Table.

  Up to Day 35

• Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35

  An AE is any untoward medical occurrence that occurs in a participant. An AE can be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with treatment, whether considered related to the product. AEs may include the onset of new illness or undesirable medical condition or the exacerbation of pre-existing medical conditions.

  Up to Day 35

• Number of Participants With Serious Adverse Events Through Day 35

  A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is an important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent one of the other outcomes.

  Up to Day 35

• Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through Day 28

  Participants who progressed to a moderate or severe disease category or higher (Bill \& Melinda Gates Medical Research Institute \[Gates MRI\] ordinal scale ≥3) are reported. Gates MRI scale scores are assessed on a 7-point scale: 1=Asymptomatic/symptoms similar to pre-COVID-19 status; 2=Mild; 3=Moderate or severe; 4=Critically ill; 5=Critically ill with invasive mechanical ventilation or extrapulmonary complication; 6=Critically ill with Extra-Corporeal Membrane Oxygenation (ECMO); 7=Death.

  Up to Day 28

Secondary Outcomes (11)

• Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28

  Up to Day 28

• Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28

  Up to Day 28

• Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale at Day 8, 14, and 21

  Days 8, 14, and 21

• Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28

  Days 8, 14, 21, and 28

• Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at Days 8, 14, 21, and 28

  Days 8, 14, 21, and 28

Other Outcomes (2)

• Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28

  Baseline; Days 8, 14, 21, and 28

• Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28

  Baseline; Days 8, 14, 21, and 28

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

Drug: Rivaroxaban

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Rivaroxaban DRUG

Participants self-administered rivaroxaban, 10 milligrams (mg) (1 tablet) orally once daily for 21 days.

Rivaroxaban

Placebo DRUG

Participants self-administered rivaroxaban matching placebo orally once daily for 21 days.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be at high-risk for Coronavirus disease 2019 (COVID-19) disease progression by fulfilling at least one of the following criteria at screening:
• Presence of chronic pulmonary disease, chronic obstructive pulmonary disease (COPD), pulmonary hypertension
• Diabetes mellitus (type 1 or type 2), requiring oral medication or insulin for treatment
• Hypertension, requiring at least one oral medication for treatment
• Immunocompromised status due to disease (e.g., those living with human immunodeficiency virus with a cluster of differentiation 4 \[CD4\] T-cell count of \<200 per cubic millimeter \[mm\^3\])
• Immunocompromised status due to medication (e.g., taking 20 milligram \[mg\] or more of prednisone equivalents a day, anti-inflammatory monoclonal antibody therapies, cancer therapies)
• Any chronic disease that is associated with high risk for severe COVID in the opinion of the site investigator
• Body mass index ≥35 Kilogram per square meter (kg/m\^2) (based on self-reported weight and height).
• Documented Severe Acute Respiratory Syndrome Coronavirus 2 positive diagnostic test of ≤7 days at the time of screening
• Symptomatic for COVID-19 for ≤72 hours at the time of screening (defined as having at least 2 of the following symptoms of COVID-19 that is of new onset or has worsened from baseline, and include fever, chills, myalgia, arthralgia, headache, fatigue, cough, sore throat, nasal congestion, anosmia, ageusia, nausea, vomiting, or diarrhea. If only two symptoms are present, they cannot both be anosmia and ageusia)
• Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the inform consent form and in this protocol
• Agree to participate in all remote, in-person or home visits as required in the protocol and provide updated contact information as necessary.
• Female of childbearing potential must agree to practice adequate contraception during the study

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Currently hospitalized or under immediate consideration for hospitalization at screening and Day 1
• Have new onset shortness of breath or increased shortness of breath from pre-COVID-19 (for people with known COPD) at screening and Day 1
• Hypoxemia (oxygen saturation \<94% in ambient air or oxygen saturation below pre-COVID-19 level for people with known COPD) at Day 1
• Require supplemental oxygen (new requirement or increase in requirement from pre-COVID-19 condition) at screening and Day 1
• Have a history of (in the past 3 months) or current active pathological bleeding
• Have a history of hemorrhagic stroke or intracranial hemorrhage
• Have a recent severe head trauma within 30 days which includes concussion, skull fracture or hospitalization for head injury
• Have known intracranial neoplasm, cerebral metastases, arteriovenous malformation or aneurysm
• Have history of pregnancy-related hemorrhage
• Have active gastroduodenal ulcer or other gastrointestinal bleeding diagnosed in the past 3 months
• Currently are in a hemodynamically unstable state
• Currently require thrombolysis or pulmonary embolectomy
• Have history of severe hypersensitivity reaction to Xarelto®
• Currently have a prosthetic heart valve

Sponsors & Collaborators

• Gates Medical Research Institute: lead

Study Sites (20)

Woodland Research Northwest LLC - ERG - PPDS

Rogers, Arkansas, 72758, United States

Location

Science 37, Inc

Los Angeles, California, 90094, United States

Location

Allergy and Asthma Medical Group and Research Center - CRN - PPDS

San Diego, California, 92123, United States

Location

Invesclinic, LLC

Fort Lauderdale, Florida, 33308, United States

Location

Advanced Pulmonary Research Institute

Loxahatchee Groves, Florida, 33470, United States

Location

LCC Medical Research - Miami - BTC - PPDS

Miami, Florida, 33126, United States

Location

Adult Medicine of Lake County

Mt. Dora, Florida, 32757, United States

Location

Providea Health Partners LLC

Evergreen Park, Illinois, 60805, United States

Location

Clinical Research Institute, Inc - CRN - PPDS

Minneapolis, Minnesota, 55402, United States

Location

Encompass Care

North Las Vegas, Nevada, 89086, United States

Location

Riverside Medical Group - Circuit- PPDS

Secaucus, New Jersey, 07094, United States

Location

Elmhurst Hospital Center

Elmhurst, New York, 11373, United States

Location

Harlem Hospital Center

New York, New York, 10037, United States

Location

NYC Health + Hospitals/Lincoln

The Bronx, New York, 10451, United States

Location

Premier Family Physicians - Austin - Hunt - PPDS

Austin, Texas, 78735, United States

Location

Village Health Partners - Plano - Hunt - PPDS

Plano, Texas, 75024, United States

Location

South Texas Allergy and Asthma Medical Professionals

San Antonio, Texas, 78229, United States

Location

Boundary House Medical Centre

Sale, Cheshire, M33 2RH, United Kingdom

Location

St Mary's Hospital - PPDS

London, City of London, W2 1NY, United Kingdom

Location

Royal Free Hospital

London, NW3 2Q, United Kingdom

Location

Related Publications (2)

• Santos BC, Flumignan RL, Civile VT, Atallah AN, Nakano LC. Prophylactic anticoagulants for non-hospitalised people with COVID-19. Cochrane Database Syst Rev. 2023 Aug 16;8(8):CD015102. doi: 10.1002/14651858.CD015102.pub2.

  PMID: 37591523 DERIVED

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

  PMID: 35244208 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Based on Data Monitoring Committee's recommendation on 3 February 2021, the study was stopped on 4 February 2021 due to futility.

Results Point of Contact

• Title: Study Director
• Organization: Gates MRI

clinical.trials@gatesmri.org

+1 857 702 2108

Study Officials

• GatesMRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2020
• First Posted: August 7, 2020
• Study Start: September 2, 2020
• Primary Completion: March 10, 2021
• Study Completion: March 29, 2021
• Last Updated: October 22, 2021
• Results First Posted: October 22, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

US (17); GB (3)