D-dimer Adjusted Versus Therapeutic Dose Low-molecular-weight Heparin in Patients With COVID-19 Pneumonia

evaluation of the efficacy and safety of D-dimer adjusted heparin versus therapeutic dose heparin in patients with COVID-19 Pneumonia.

Study Overview

• Status: Unknown
• Conditions: Coronavirus Disease (COVID)19
• Intervention / Treatment: Drug: low-molecular-weight heparin

Detailed Description

The following will be done for enrolled patients:

1. Data collection: name, age, sex, special habits of medical importance (i.e. smoking, drug abuse), comorbid conditions.
2. Clinical examination Vital data Local chest examination
3. Measurement of oxygen saturation using pulse oximeter

4. Laboratory investigations:

   Complete blood count with differential count Liver and kidney functions D-dimer level Coagulation profile

5. Radiology work up ( Chest X-ray-High resolution computed tomography of the chest- computed tomography of the chest with pulmonary angiography as needed)
6. Sepsis-induced coagulopathy score (SIC score)
7. Sequential organ failure score (SOFA score)
8. Patients will receive treatment according to the hospital guidelines for different disease stratification severity

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ashraf Madkour; Phone Number: +20 100 177 0703; Email: asfrah_madkour@yahoo.com

Study Locations

• Egypt
  • Non-US
    • Cairo, Non-US, Egypt, 11566
      • Recruiting
      • Faculty of Medicine Ain Shams University Research Institute- Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult (>18 years) patients from both sexes with COVID-19 pneumonia with positive nucleic acid test for severe acute respiratory syndrome Coronavirus (SARS-CoV-2) hospitalized either in the ward or intensive care unit

Exclusion Criteria:

• Patients with absolute contraindication of pharmacological thromboprophylaxis and/ anticoagulation
• Congenital hemorrhagic disorders
• Hypersensitivity to heparin
• Personal history of heparin-induced thrombocytopenia
• Active major bleeding or conditions predisposing to major bleeding. Major bleeding is defined as fulfilling any one of these three criteria: a) occurs in a critical area or organ (e.g.intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, intra-uterine or intramuscular with compartment syndrome), b) causes a fall in haemoglobin level (Hb) of ≥2g/dL in a 24h period, or c) leads to transfusion of 2 or more units of whole blood or red blood cells (13).
• Suspected or confirmed bacterial endocarditis
• Ongoing or planned therapeutic anticoagulation for any other indication
• Platelet count <50,000/μL within the past 24 hours or Hb level <8g/dL
• Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours
• Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours
• Fibrinogen <2.0 g/L
• Severe renal impairment (CrCl<30 mL/min) or acute kidney injury
• Use of dual antiplatelet therapy
• Pregnancy
• Unwillingness to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapeutic dose low-molecular-weight heparin (LMWH); Therapeutic dose low-molecular-weight heparin from admission until the end of hospital stay Enoxaparin 1 mg/kg subcutaneous every 12 hours	Drug: low-molecular-weight heparin; low-molecular-weight heparin administered via subcutaneous injection; Other Names: Enoxaparin
Experimental: D-dimer levels and weight adjusted low-molecular-weight heparin (LMWH)therapy; from admission until the end of hospital stay. Patients will be stratified according to their body weight and D-dimer level and receive LMWH D-Dimer level Body Weight LMWH dose <1 mg/dl <100kg Enoxaparin 40mg OD 100-150kg Enoxaparin 40mg BD >150kg Enoxaparin 60mg BD 1-3 mg/ dl <100kg Enoxaparin 40mg BD 100-150kg Enoxaparin 80mg BD >150kg Enoxaparin 120mg BD >3 mg/ dl Enoxaparin 80mg BD	Drug: low-molecular-weight heparin; low-molecular-weight heparin administered via subcutaneous injection; Other Names: Enoxaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	All cause mortality	Until patient is discharged or up to 4 weeks whichever comes first
occurrence of venous and/or arterial thrombosis	clinical signs supported by radiological evidence of arterial thrombosis or venous thromboembolism (e.g. venous or arterial duplex and CT scan of the chest with pulmonary angiography)	Until patient is discharged or up to 4 weeks whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurrence of Sepsis-induced coagulopathy	calculation of sepsis induced coagulopathy (SIC) score	Until patient is discharged or up to 4 weeks whichever comes first
Occurrence of adult respiratory distress syndrome (ARDS)	Calculation of partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/ FIO2) ratio	Until patient is discharged or up to 4 weeks whichever comes first
Occurrence of sepsis	Calculation of sequential organ failure (SOFA) score	Until patient is discharged or up to 4 weeks whichever comes first
ICU admission and need for mechanical ventilation	occurrence of respiratory failure detected by arterial blood gases analysis	Until patient is discharged or up to 4 weeks whichever comes first

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Ashraf Madkour, Ain Shams University, Faculty of Medicine

Publications and helpful links

General Publications

• Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): October 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 6, 2020
• First Submitted That Met QC Criteria: October 10, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 10, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: FMASU P35/ 2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No