Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19 (COVID-PREVENT)
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|ClinicalTrials.gov Identifier: NCT04416048|
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : June 9, 2021
Patients with moderate to severe COVID-19 present a very high risk of thromboembolic disease.This multicenter, prospective, randomized, event-driven study evaluates rivaroxaban compared with standard of care including low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) at prophylactic doses if applicable in the prevention of the composite of venous thromboembolism (deep vein thrombosis and/or fatal or non-fatal pulmonary embolism), arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause mortality or progression to intubation and invasive ventilation 35 days post randomization in patients with moderate to severe COVID-19.
Experimental intervention/Index test:
Patients randomized into the rivaroxaban arm will receive rivaroxaban 20 mg once daily (OD) until day 7 post randomization or hospital discharge, whichever occurs later, followed by a 28-day-phase of prophylactic anticoagulation with rivaroxaban 10mg OD. Subjects with an eGFR between 30 and 50ml/min/1,73m2, will receive 15mg instead of 20mg OD.
Control intervention/Reference test:
The control group will receive standard of care including LMWH or UFH as thromboprophylaxis or no anticoagulation, if appropriate.
Duration of intervention per patient:
The total duration of the study treatment is flexible. For out-patients 7 days of therapeutic anticoagulation will be accompanied by 28 days-phase of prophylactic anticoagulation, summing up to 35 days. For subjects that require hospitalization, the duration of therapeutic anticoagulation will be at least 7 days or prolonged until discharge if hospitalized for more than 7 days post randomization.
After discharge from the hospital the subject receives 28 days of thromboprophylaxis with rivaroxaban. No study medication will be given past day 60 post randomization. This adds up to a study duration between 35 and 60 days depending on the duration of the hospital stay.
Follow-up per patient:
The study has a follow-up of 60 days.
Experimental and/or control off label or on label in Germany:
Rivaroxaban has been approved for multiple indications worldwide. Over 100,000 subjects have been studied from Phase 1 through multiple large Phase 4 studies in multiple settings, e.g. for the reduction in the risk of stroke and systemic embolism in arterial fibrillation, deep vein thrombosis and pulmonary embolism, major cardiovascular events. The drug had not been studied in patients with COVID-19 as an anticoagulant agent, yet.
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Rivaroxaban Other: Standard Of Care (SOC)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||400 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||A multicenter, prospective, randomized, event-driven study.|
|Masking:||None (Open Label)|
|Masking Description:||Central randomization will be implemented in this study. Subjects will be randomly assigned to 1 of 2 treatment groups based on a computer-generated randomization schedule prepared before the study under the supervision of the sponsor. The randomization will be stratified by site, gender, age, kidney function (subjects with eGFR ≥30 mL/min/1.73m2 and <50 mL/min/1.73m2 versus subjects with eGFR ≥50 mL/min/1.73m2), history of CAD or heart failure and oxygen demand on admission to the hospital. The computer system will assign a unique treatment code, which will dictate the treatment assignment and study drug kits for the subject. The requestor must use his or her own user identification and personal identification number when contacting the system and will then give the relevant subject details to uniquely identify the subject.|
|Official Title:||Effect of Anticoagulation Therapy on Clinical Outcomes in Moderate to Severe Coronavirus Disease 2019 (COVID-19)|
|Actual Study Start Date :||November 30, 2020|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||January 31, 2022|
Subjects will receive treatment with rivaroxaban. (for more information see intervention description)
Treatment with Rivaroxaban 20 mg (15 mg for subjects with an eGFR ≥30 mL/min/1.73m2 and <50 mL/min/1.73m2) once daily (OD) for at least 7 days. In case of hospitalization for more than 7 days, the therapeutic treatment with rivaroxaban will be continued for the duration of the hospital stay until discharge. After at least 7 days of therapeutic treatment with rivaroxaban or after hospital discharge, the study dose of rivaroxaban will be adjusted as follows. Patients randomized to the rivaroxaban study arm will reduce daily dosage to 10 mg OD, provided that they were not diagnosed with a condition requiring continued therapeutic anticoagulation. Thromboprophylaxis therapy will be given for 28 days up to day 35 post randomization or even longer. If the patient cannot be discharged from the hospital prior to day 35 post randomization, the thromboprophylaxis phase will also start upon hospital discharge, but is then shorter than 28 days, because the study ends at day 60 post randomization.
Other Name: XARELTO®
Standard of Care
Subjects will receive standard of care (SOC) treatment SOC including prophylactic LMWH or UFH, when considered appropriate according to the judgment of the treating physician.
Other: Standard Of Care (SOC)
Standard of care treatment
- Composite endpoint of venous thromboembolism (DVT and/or fatal or non-fatal PE), arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause mortality or progression to intubation and invasive ventilation [ Time Frame: 35 days post randomization ]
- Development of disseminated intravascular coagulation (DIC) according to the ISTH criteria [ Time Frame: 35 days post randomization ]
- Number of days requiring invasive ventilation [ Time Frame: 35 days post randomization ]
- Number of days requiring non-invasive ventilation [ Time Frame: 35 days post randomization ]
- Improvement on a seven-category ordinal scale recommended by the WHO as clinical improvement scale for patients with respiratory infections [ Time Frame: 35 days post randomization ]scale range from 1 to 7; improvement means a reduction in the scale number of at least one point
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): NCT04416048
|Contact: Ulf Landmesser, Prof. Dr.||+49 30 450 513 email@example.com|
|Contact: Ursula Rauch-Kroehnert, Prof. Dr. med.||+49 30 450 513 firstname.lastname@example.org|
|Principal Investigator:||Ulf Landmesser, Prof. Dr.||Charite University, Berlin, Germany|
|Principal Investigator:||Co-PI: Andreas M. Zeiher, Prof. Dr.||Johann Wolfgang Goethe-University, Frankfurt am Main, Germany|
|Principal Investigator:||Co-PI: Steffen Massberg, Prof. Dr.||Ludwig-Maximilians - University of Munich|
|Principal Investigator:||Co-PI: Ursula Rauch-Kröhnert, Prof. Dr.||Charité University, Berlin, Germany|
|Principal Investigator:||Co-PI: Jan Beyer-Westendorf, Prof. Dr.||University Hospital Carl Gustav Carus at the Technical University of Dresden|