Intermediate-dose vs Standard Prophylactic Anticoagulation and Statin vs Placebo in ICU Patients With COVID-19

• Status: Completed
• Trial end date: 2021-07-05
• Target enrollment: 0
• Participant gender: All

Summary

In a 2x2 factorial design randomized controlled trial, the investigators aim to elaborate the safety and efficacy of two pharmacological regimens on outcomes of critically-ill patients with COVID-19. The first randomization entails open-label assignment to intermediate versus standard dose prophylactic anticoagulation. The investigators hypothesize that intermediate dose compared with standard prophylactic dose anticoagulation will have a superior efficacy with respect to a composite of venous thromboembolism (VTE), requirement for extracorporeal membrane oxygenation (ECMO), or all-cause mortality. The second randomization will be double-blind assignment of the included patients to atorvastatin 20mg daily versus matching placebo. The hypothesis is that statin therapy, compared with placebo, will reduce the composite of VTE, need for ECMO, or all-cause mortality.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rajaie Cardiovascular Medical and Research Center
• Collaborators: Brigham and Women's Hospital; Firuzgar hospital affiliated to Iran University of Medical Sciences; Hazrat Rasool Hospital; Imam Ali Hospital; Imam Khomeini Hospital; Labbafinejhad Hospital; Masih Daneshvari Hospital; Modarres Hospital; Shariati Hospital; Sina Hospital, Iran; Tabriz University of Medical Sciences; Tehran Heart Center
• Treatments: Atorvastatin; Calcium heparin; Enoxaparin; Enoxaparin sodium; Heparin; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Criteria

Inclusion Criteria for Anticoagulation Hypothesis

1. Adult patients (≥18 years), with polymerase chain reaction (PCR)-confirmed COVID-19 admitted to ICU within 7 days of initial hospitalization , who do not have another firm indication for anticoagulation (such as mechanical valve, high-risk atrial fibrillation (AF), VTE, or left ventricle (LV) thrombus),who are not enrolled in another blinded randomized trial, and are willing to participate in the study and provide informed consent .

2. Estimated survival of at least 24 hours at the discretion of enrolling physician

Exclusion Criteria for Anticoagulation Hypothesis

1. Weight <40 Kilogram (kg)

2. Overt bleeding at the day of enrollment

3. Known major bleeding within 30 days (according to the Bleeding Academic Research Consortium (BARC) definition, Appendix A)

4. Platelet count <50,000/Fl

5. Pregnancy (as confirmed by Beta human chorionic gonadotropin (HCG) testing among female patients <50 years)

6. Patients on Extracorporeal Membrane Oxygenation (ECMO)

7. History of heparin induced thrombocytopenia or immune thrombocytopenia

8. Ischemic stroke within the past 2 weeks

9. Craniotomy/major neurosurgery within the past 3 months

10. Major head or spinal trauma in the past 30 days

11. Known brain metastases or vascular malformations (aneurysm)

12. Presence of an epidural, spinal or pericardial catheter

13. Major surgery other than neurosurgery within 14 days prior to enrollment

14. Coexistence of severe obesity (weight >120 kg or BMI>35 kg/m2 along with severe renal insufficiency defined as creatinine clearance (CrCl) <30 mL/sec)

15. Allergic reaction to study medications

16. Lack or withdrawal of informed consent

Inclusion Criteria for the Statin Randomization

1. Patients enrolled for the anticoagulation randomization

2. Willingness to participation in the study and providing informed consent

Exclusions Criteria for the Statin Randomization

1. Baseline liver function tests> 3 times upper normal limits (ULN) or creatine kinase (CK) >500 U/L

2. Active liver disease (LFT>3 ULN plus histologic finding including cirrhosis or inflammation or necrosis)

3. Routine use of statins prior to the index hospitalization

4. Previous documented statin intolerance