Clinical Trials Logo

Clinical Trial Summary

Coagulopathy of COVID-19 afflicts approximately 20% of patients with severe COVID-19 and is associated with need for critical care and death. COVID-19 coagulopathy is characterized by elevated D-dimer, an indicator of fibrin formation and clot lysis, and a mildly prolonged prothrombin time, suggestive of coagulation consumption. To date, it seems that COVID-19 coagulopathy manifests with thromboembolism, thus anticoagulation may be of benefit. We propose to conduct a parallel pragmatic multi-centre open-label randomized controlled trial to determine the effect of therapeutic anticoagulation compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer.


Clinical Trial Description

2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine the effect of therapeutic anticoagulation, with low molecular weight heparin or unfractionated heparin (high dose nomogram), compared to standard care in hospitalized patients with COVID-19 and an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Eligible participants will be randomized to one of two treatment regimens, receiving either therapeutic anticoagulation or standard care until discharged from hospital, death or day 28. The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation, or all-cause death up to 28 days. Key secondary outcomes between study arms up to day 28 include: 1. All-cause death 2. Composite outcome of ICU admission or all-cause death 3. Composite outcome of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation 5. Number of participants who received red blood cell transfusion (≥1 unit) 6. Number of participants with transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate 7. Renal replacement therapy; 8. Number of hospital-free days alive 9. Number of ICU-free days alive 10. Number of ventilator-free days alive 11. Number of organ support-free days alive 12. Number of participants with venous thromboembolism 13. Number of participants with arterial thromboembolism 14. Number of participants with heparin induced thrombocytopenia 15. Changes in D-dimer up to day 3 The treatment arm is therapeutic anticoagulation with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin, or Dalteparin. UFH will be administered using a weight-based nomogram with titration according to the center-specific protocol. Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the patient is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement. The standard care arm is the administration of LMWH, UFH or fondaparinux at thromboprophylactic doses in the absence of contraindication. No study specific bloodwork will be ordered aside from a single D-dimer test (if not collected through standard of care) up to and including day 3 after randomization for all participants in both study arms. In those on the active treatment arm who are receiving UFH, the aPTT or UFH anti-Xa will be drawn according to local institutional UFH nomogram protocol guidance. All laboratory results will be collected from standard of care from admission to hospital discharge, death or 28 days, where available. An optional biobanking component will collect blood at baseline and 2 follow up time points. This study will immediately impact the clinical care of patients with severe COVID-19 internationally, whether the findings are positive or negative, as COVID-19 coagulopathy is a highly prevalent complication of severe COVID-19 and may precede the respiratory manifestations that characterize it. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04444700
Study type Interventional
Source University of Sao Paulo General Hospital
Contact
Status Completed
Phase Phase 3
Start date July 4, 2020
Completion date October 14, 2021

See also
  Status Clinical Trial Phase
Terminated NCT04558125 - Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism Phase 4
Recruiting NCT04410510 - P2Et Extract in the Symptomatic Treatment of Subjects With COVID-19 Phase 2/Phase 3
Active, not recruiting NCT04420676 - Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection N/A
Completed NCT04419025 - Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease Phase 2
Completed NCT04395911 - Safety and Efficacy of SCD in AKI or ARDS Patients Associated With COVID-19 Infections N/A
Completed NCT04425317 - Detection of SARS-CoV-2 in Follicular Fluid and Cumulus-oocyte-complexes in COVID-19 Patients N/A
Completed NCT04526769 - Detecting SARS-CoV-2 in Tears
Withdrawn NCT04456426 - Characteristics of Patients With COVID-19 in Meta State, Colombia
Completed NCT04425720 - Use of Remote Monitoring for COVID-19 Patient N/A
Suspended NCT04385771 - Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation N/A
Completed NCT04419610 - RAS and Coagulopathy in COVID19 Early Phase 1
Completed NCT04546581 - Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC) Phase 3
Completed NCT04435327 - Lung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19)
Terminated NCT04530448 - Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization Phase 4
Not yet recruiting NCT04524156 - COVID-19 : Transcutaneous pO2 and pCO2 as Predictive Factors for Acute Respiratory Destress Syndrome in Patients Affected With SARS-Cov-2 N/A
Completed NCT04441710 - Caregiver Serological Monitoring Extended Secondarily to Patients With the SARS-CoV-2 Coronavirus
Completed NCT04357834 - WAVE. Wearable-based COVID-19 Markers for Prediction of Clinical Trajectories
Not yet recruiting NCT04392427 - New Antiviral Drugs for Treatment of COVID-19 Phase 3
Terminated NCT04614025 - Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 Phase 2
Completed NCT04402957 - LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19) Phase 2