NCT04416048: COVID-PREVENT

Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19

Terminated Phase 2 Last updated 12 January 2022

What this trial tests

Phase 2 trial testing Rivaroxaban in COVID-19 in 111 participants. Terminated before completion.

Timeline

30 November 2020

Primary endpoint
20 July 2021

20 July 2021

Quick facts

Lead sponsor	Charite University, Berlin, Germany
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	111
Start date	30 November 2020
Primary completion	20 July 2021
Estimated completion	20 July 2021
Sites	24 locations across Germany

Drugs / interventions tested

• Rivaroxaban (rivaroxaban) — full drug profile →
• Standard Of Care (SOC) — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Charite University, Berlin, Germany

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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 with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) at prophylactic doses comparing D-dimer levels and the seven-category ordinal scale recommended by the WHO 7 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.

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Post-acute COVID-19 syndrome.
   Nalbandian A, Sehgal K, Gupta A, Madhavan MV, et al · · 2021 · cited 3355× · PMID 33753937 · DOI 10.1038/s41591-021-01283-z
2. Long-term complications of COVID-19.
   Desai AD, Lavelle M, Boursiquot BC, Wan EY. · · 2022 · cited 248× · PMID 34817268 · DOI 10.1152/ajpcell.00375.2021
3. Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis.
   Porfidia A, Valeriani E, Pola R, Porreca E, et al · · 2020 · cited 165× · PMID 32853978 · DOI 10.1016/j.thromres.2020.08.020
4. Coronavirus Disease 2019-Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management.
   Ortega-Paz L, Capodanno D, Montalescot G, Angiolillo DJ. · · 2021 · cited 112× · PMID 33228447 · DOI 10.1161/jaha.120.019650
5. Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration.
   Tritschler T, Mathieu ME, Skeith L, Rodger M, et al · · 2020 · cited 77× · PMID 32888372 · DOI 10.1111/jth.15094
6. Prothrombotic changes in patients with COVID-19 are associated with disease severity and mortality.
   von Meijenfeldt FA, Havervall S, Adelmeijer J, Lundström A, et al · · 2021 · cited 67× · PMID 33537537 · DOI 10.1002/rth2.12462
7. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
   Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
8. Incidence of symptomatic, image-confirmed venous thromboembolism following hospitalization for COVID-19 with 90-day follow-up.
   Salisbury R, Iotchkova V, Jaafar S, Morton J, et al · · 2020 · cited 56× · PMID 33351117 · DOI 10.1182/bloodadvances.2020003349