Clinical trial NCT04504032: A Trial to Evaluate Safety and Efficacy of Rivaroxaban (COVID-19)
Official title: A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Rivaroxaban
Xarelto
Coronavirus
COVID-19
Coronavirus disease 2019
Lead sponsor: Bill & Melinda Gates Medical Research Institute
Sponsor class: OTHER
First posted: 2020-08-07
Enrollment: 497
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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
* Have known diagnosis of triple positive antiphospholipid syndrome
* Have known diagnosis of chronic kidney disease (stage IV or receiving dialysis)
* Have a history of thrombocytopenia or known platelet count \<100,000 cells/mm\^3
* Have history of bronchiectasis and pulmonary cavitation
* Have active cancer (e.g, receiving chemotherapy or treatment for complication of the active cancer)
* Had epidural or neuraxial anesthesia or spinal puncture in the past 2 weeks and plan to undergo these procedures during the study
* Had surgery in the past 4 weeks or plan to undergo surgery during the study
* Currently is pregnant or plans to become pregnant
* Currently is breastfeeding
* Share household with an enrolled participant in this study
* Co-enrollment in any clinical trial that includes prohibited procedures (spinal puncture or surgery) or that includes treatments within the same drug class as rivaroxaban or treatments for which co-administration with rivaroxaban are prohibited. Note that any co-enrollment other than this requires approval by the Sponsor. For any co-enrolled study, the total volume of blood samples collected across the studies should not exceed 275 milliliters (mL) in 4 weeks.
* Currently using and plan to use the following medications during the study

  * Rivaroxaban or drugs in the same class
  * Dual anti-platelets therapy
  * Other anticoagulants
  * Combined Permeability glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) inhibitors and inducers

Primary outcomes:
measure: Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) Through Day 35
timeFrame: Up to Day 35
measure: Number of Participants With AEs Resulting in Study Intervention Discontinuation Through Day 35
timeFrame: Up to Day 35
measure: Number of Participants With Serious Adverse Events Through Day 35
timeFrame: Up to Day 35
measure: Number of Participants Who Progressed to Moderate or Severe Disease or Higher Based on the Gates MRI Ordinal Scale Through Day 28
timeFrame: Up to Day 28
Secondary outcomes:
measure: Median Time to Disease Resolution Based on Symptoms Resolution Through Day 28
timeFrame: Up to Day 28
measure: Median Time to Disease Resolution Based on Viral Clearance and Symptoms Resolution Through Day 28
timeFrame: Up to Day 28
measure: 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
timeFrame: Days 8, 14, and 21
measure: Number of Participants Who Achieved Disease Resolution Based on Symptoms Resolution at Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Number of Participants Who Achieved Disease Resolution Based on Viral Clearance and Symptoms Resolution at Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Number of Participants With the Indicated Gates Medical Research Institute (MRI) Scale Clinical Status at Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Number of Participants With the Indicated World Health Organization (WHO) Ordinal Scale Clinical Status at Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Number of Participants With Hospitalization Through Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Median Number of Days of Hospitalization Through Day 35
timeFrame: Up to Day 35
measure: Shift in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
timeFrame: Days 8, 14, 21, and 28
measure: Shift in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
timeFrame: Baseline; Days 8, 14, 21, and 28
Other outcomes:
measure: Change From Baseline in Gates Medical Research Institute Ordinal Scale Score at Days 8, 14, 21, and 28
timeFrame: Baseline; Days 8, 14, 21, and 28
measure: Change From Baseline in World Health Organization Ordinal Scale Score at Days 8, 14, 21, and 28
timeFrame: Baseline; Days 8, 14, 21, and 28
Locations:
city: Rogers
country: United States
facility: Woodland Research Northwest LLC - ERG - PPDS
state: Arkansas
city: Los Angeles
country: United States
facility: Science 37, Inc
state: California
city: San Diego
country: United States
facility: Allergy and Asthma Medical Group and Research Center - CRN - PPDS
state: California
city: Fort Lauderdale
country: United States
facility: Invesclinic, LLC
state: Florida
city: Loxahatchee Groves
country: United States
facility: Advanced Pulmonary Research Institute
state: Florida
city: Miami
country: United States
facility: LCC Medical Research - Miami - BTC - PPDS
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County
state: Florida
city: Evergreen Park
country: United States
facility: Providea Health Partners LLC
state: Illinois
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc - CRN - PPDS
state: Minnesota
city: North Las Vegas
country: United States
facility: Encompass Care
state: Nevada
city: Secaucus
country: United States
facility: Riverside Medical Group - Circuit- PPDS
state: New Jersey
city: Bronx
country: United States
facility: NYC Health + Hospitals/Lincoln
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: New York
country: United States
facility: Harlem Hospital Center
state: New York
city: Austin
country: United States
facility: Premier Family Physicians - Austin - Hunt - PPDS
state: Texas
city: Plano
country: United States
facility: Village Health Partners - Plano - Hunt - PPDS
state: Texas
city: San Antonio
country: United States
facility: South Texas Allergy and Asthma Medical Professionals
state: Texas
city: Sale
country: United Kingdom
facility: Boundary House Medical Centre
state: Cheshire
city: London
country: United Kingdom
facility: St Mary's Hospital - PPDS
state: City Of London
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Bill & Melinda Gates Medical Research Institute
name: GatesMRI
role: STUDY_DIRECTOR
References:
citation: 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.