Safety and Efficacy of Therapeutic Anticoagulation on Clinical Outcomes in Hospitalized Patients With COVID-19
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| ClinicalTrials.gov Identifier: NCT04377997 |
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Recruitment Status :
Not yet recruiting
First Posted : May 7, 2020
Last Update Posted : May 7, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cardiovascular Diseases COVID-19 | Drug: Enoxaparin | Phase 2 |
Patients identified as eligible through discussions with the primary care team and review of the electronic medical record will be approached and consented as described above in "Subject Enrollment" and "Procedures for obtaining consent".
For research purposes, 20mL of blood will be drawn and stored for biobanking at the following timepoints: at baseline (i.e., after enrollment and before randomization), 5-7 days post-randomization, and on the day of discharge.
After enrollment and blood collection, patients will then be randomized to therapeutic anticoagulation (LMWH for most subjects but UFH for those with morbid obesity or moderate to severe renal dysfunction as noted below) or standard of care.
Based on the MGH COVID-19 Treatment Guidance document, the risk stratification recommends daily complete blood count (CBC), comprehensive metabolic panel (CMP), creatine kinase (CPK), ferritin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). In addition, PT, PTT, fibrinogen, and D-dimer are recommended to be checked every other day if in the ICU or daily if elevated. Given that by virtue of the inclusion criteria of our study (i.e., a D-dimer >1ug/mL), all of our patients will be within Category 3 and all of the above markers will be obtained for clinical purposes and thus will also be documented for research purposes. For clinical risk stratification, LDH is to be checked daily if elevated and troponin to be checked q2-3d if elevated. If clinically indicated, procalcitonin will be measured and IL-6 obtained in patients in Category 2 or 3 disease severity. If measured for clinical purposes, LDH, troponin, procalcitonin, and IL-6 will be recorded for research purposes.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 300 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | randomized 1:1 |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Open-Label Trial of Therapeutic Anticoagulation in COVID-19 Patients With an Elevated D-Dimer |
| Estimated Study Start Date : | May 15, 2020 |
| Estimated Primary Completion Date : | January 1, 2021 |
| Estimated Study Completion Date : | January 1, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Therapeutic Anticoagulation Group
Patients identified as eligible through discussions with the primary care team and review of the electronic medical record will be approached and consented as described above in "Subject Enrollment" and "Procedures for obtaining consent". For research purposes, 20ml of blood will be drawn and stored for biobanking at the following timepoints: at baseline (i.e., after enrollment and before randomization), 5-7 days post-randomization, and on the day of discharge. The blood sample taken at baseline will also be used to conduct a pregnancy test for women of childbearing age. After enrollment and blood collection, patients will then be randomized to therapeutic anticoagulation (LMWH for most subjects but UFH for those with morbid obesity or moderate to severe renal dysfunction as noted below) or standard of care anticoagulation. Those assigned to the therapeutic anticoagulation group will receive a higher dose of heparin. |
Drug: Enoxaparin
Given the established link between endothelial dysfunction and thrombosis in patients with cardiovascular disease9, 10 and the association between coagulopathy and adverse outcomes in patients with sepsis11, the association between increased coagulation activity, end-organ injury, and mortality risk may represent a modifiable risk factor among COVID-19 patients with critical illness. Therefore, we propose to conduct a randomized, open-label trial of therapeutic anticoagulation in COVID-19 patients with an elevated D-dimer to evaluate the efficacy. Most patients will receive low molecular weight heparin however, unfractionated heparin (UFH) will be administered for those with morbid obesity or moderate to severe renal dysfunction.
Other Names:
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Active Comparator: Standard of Care Anticoagulation Group
Patients identified as eligible through discussions with the primary care team and review of the electronic medical record will be approached and consented as described above in "Subject Enrollment" and "Procedures for obtaining consent". For research purposes, 20ml of blood will be drawn and stored for biobanking at the following timepoints: at baseline (i.e., after enrollment and before randomization), 5-7 days post-randomization, and on the day of discharge. The blood sample taken at baseline will also be used to conduct a pregnancy test for women of childbearing age. After enrollment and blood collection, patients will then be randomized to therapeutic anticoagulation or standard of care anticoagulation. Those assigned to the standard of care anticoagulation group will receive the normal dose of heparin as per the Mass General guidelines. |
Drug: Enoxaparin
Given the established link between endothelial dysfunction and thrombosis in patients with cardiovascular disease9, 10 and the association between coagulopathy and adverse outcomes in patients with sepsis11, the association between increased coagulation activity, end-organ injury, and mortality risk may represent a modifiable risk factor among COVID-19 patients with critical illness. Therefore, we propose to conduct a randomized, open-label trial of therapeutic anticoagulation in COVID-19 patients with an elevated D-dimer to evaluate the efficacy. Most patients will receive low molecular weight heparin however, unfractionated heparin (UFH) will be administered for those with morbid obesity or moderate to severe renal dysfunction.
Other Names:
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- Number of patients with the composite efficacy endpoint of death, cardiac arrest, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, or hemodynamic shock. [ Time Frame: 12 weeks ]Aim 1 - Risk of death, cardiac arrest, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, or hemodynamic shock.
- Number of patients with a major bleeding event according to the International Society on Thrombosis and Haemostasis (ISTH) definition. [ Time Frame: 12 weeks ]Aim 2 - Risk of major bleeding event according to the International Society on Thrombosis and Haemostasis (ISTH) definition.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion:
- COVID-19 positive on admission or during hospitalization (having been tested within the past 5 days) with symptoms consistent with COVID-19 including fever (≥ 38C, 100.4F), pneumonia, symptoms of lower respiratory illness (e.g., cough, difficulty breathing), loss of smell or taste, myalgias, pharyngitis, or diarrhea
- Admitted to the regular medical floor or intensive care unit (ICU) without severe ARDS (P/F ratio<100)
- Elevated D-dimer (>1.5g/mL)
- Age>18 years and not older than 90
- Fibrinogen >100
- Platelets >50,000
- No prior intracranial hemorrhage or recent ischemic stroke or TIA within 6 months
- D-dimer > 1500 ng/ml
- No other clinical indication for therapeutic anticoagulation (e.g., deep vein thrombosis [DVT], pulmonary embolism [PE], atrial fibrillation, acute coronary syndromes, or extracorporeal membrane oxygenation)
Exclusion:
- Disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Hemostasis overt DIC definition
- Hemoglobin (Hgb) <8 g/dl
- Hypersensitivity to heparin or heparin formulation including heparin-induced thrombocytopenia
- Thrombocytopenia: platelets<50,000 platelets/ul
- Uncontrolled or active/recent bleeding including intracranial hemorrhage, signs of active bleeding (e.g., blood transfusion within 30 days), any GI bleed within the past 6 months, or internal bleeding within the past 1 month
- High bleeding risk: significant closed-head or facial trauma within 3 months, traumatic or prolonged CPR (>10min), or use of dual anti-platelet therapy
- Known or suspected pregnancy
- Recent (<48 hours) or planned spinal or epidural anesthesia or puncture
- If the patient is on other anticoagulants, antihistamines, nonsteroidal anti-inflammatory drugs (i.e. aspirin) or hydroxychloroquine
- Uncontrolled hypertension
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): NCT04377997
| Contact: Mazen Albaghdadi, MD | 617-726-7400 | MALBAGHDADI@mgh.harvard.edu | |
| Contact: Jaclyn Pagliaro, MPH | 617-726-1525 | jaclyn.pagliaro@mgh.harvard.edu |
| Principal Investigator: | Mazen Albaghdadi, MD | Massachusetts General Hospital |
Other Publications:
| Responsible Party: | Mazen Albaghdadi, Interventional Cardiologist, Massachusetts General Hospital |
| ClinicalTrials.gov Identifier: | NCT04377997 |
| Other Study ID Numbers: |
2020P001136 |
| First Posted: | May 7, 2020 Key Record Dates |
| Last Update Posted: | May 7, 2020 |
| Last Verified: | May 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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Cardiovascular Diseases Heparin Calcium heparin Enoxaparin Heparin, Low-Molecular-Weight Tinzaparin |
Dalteparin Anticoagulants Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action |