Clinical Trial on the Efficacy and Safety of Bemiparin in Patients Hospitalized Because of COVID-19

A Randomized, Single-blind Study With a Parallel Control Group on the Efficacy and Safety of Bemiparin at Therapeutic Dose vs. Prophylactic Dose in Patients Hospitalized for COVID-19

The 2019 coronavirus disease (Covid-19) is a new disease caused by the SARS-CoV2 virus of which many things are not yet known. Among others, there is a need to define the best therapeutic strategy to treat Covid-19, improving patients survival and reducing complications in its management, for which many different types of treatments are being tested.

The drug being tested in this clinical trial is called bemiparin. Bemiparin is a drug authorized as a prevention and as a treatment for deep vein thrombosis (blood clots in one or more veins, generally in the legs) and venous thromboembolism (when the clot can detach and lodge in other organs such as the lungs). Covid-19 patients have been shown to be at increased risk of developing clotting problems such as those described above.

In this context, this clinical trial is being carried out to find out if certain doses of bemiparin can contribute to better management of the disease.

Study Overview

• Status: Terminated
• Conditions: Covid-19
• Intervention / Treatment: Drug: Bemiparin; Drug: Bemiparin

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Boadilla Del Monte, Madrid, Spain, 28660
      • Hospital Universitario HM Monteprincipe
    • Móstoles, Madrid, Spain, 28938
      • Hospital Universitario Hm Puerta Del Sur

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:

1. Informed consent.
2. Age of 18 years or more.
3. Patient with suspected COVID-19 and who meets hospitalization criteria.
4. D-dimer> 500 ng / ml.
5. Clinical characteristics highly compatible with SARS-CoV-2 infection and confirmation by RT-qPCR at baseline or in the second sample in case of a first negative test and clinical suspicion remains.
6. Patient admitted to hospital

Exclusion Criteria:

1. ICU admission criteria.
2. Need for invasive or not invasive mechanical ventilation
3. Pregnancy.
4. Creatine clearance <30 ml / min (Cockroft-Gault).
5. Severe liver or pancreatic function disorder.
6. Acute bacterial endocarditis and slow endocarditis.
7. Patient previously anticoagulated (although it is allowed to have received heparin at a previous low dose without time limit).
8. Patient with high hemorrhagic risk due to previous medical-surgical history.
9. Severe thrombocytopenia (<80,000 platelets/ mm3) or known history of heparin-induced thrombocytopenia.
10. Active bleeding or increased risk of bleeding from haemostasis disorders or from organic lesions that are liable to bleed (eg, active peptic ulcer, hemorrhagic stroke, aneurysms, or brain malignancies).
11. Damage or surgical interventions in the central nervous system, eyes and ears that have taken place in the last 2 months.
12. Simultaneous participation in another clinical trial that could have a conflictive interaction with what it is intended to evaluate.
13. Any situation that in the opinion of the researcher could interfere with the treatment or with the evolution of the patient.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental - therapeutic bemiparin dose; Sub-cutaneous dose of bemiparin at therapeutic dose for 10 days	Drug: Bemiparin; Bemiparin at therapeutic dose for 10 days; Other Names: Therapeutic dose; Drug: Bemiparin; Bemiparin at prophylactic dose for 10 days; Other Names: Prophylactic dose
Experimental: Control - prophylactic bemiparin dose; Sub-cutaneous dose of bemiparin at prophilactic dose for 10 days	Drug: Bemiparin; Bemiparin at therapeutic dose for 10 days; Other Names: Therapeutic dose; Drug: Bemiparin; Bemiparin at prophylactic dose for 10 days; Other Names: Prophylactic dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients that worsen	Combined worsening variable. Presence of any of the following will be considered worseing: Death.; ICU admission.; Need for either non-invasive or invasive mechanical ventilation.; Progression to moderate / severe respiratory distress syndrome according to objective criteria (Berlin definition).; Venous thromboembolism (deep vein thrombosis or pulmonary embolism) or arterial (acute myocardial infarction or stroke).	Day 10 +/- 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality from any cause at day 28	Mortality from any cause	Day 28
Proportion of subjects that requires admission to the ICU	Proportion of subjects that requires admission to the ICU	From study start to day 28
Proportion of subjects requiring non-invasive mechanical ventilation	Proportion of subjects requiring non-invasive mechanical ventilation	From study start to day 28
Proportion of subjects requiring invasive mechanical ventilation.	Proportion of subjects requiring invasive mechanical ventilation.	From study start to day 28
Proportion of subjects with some organ failure	Proportion of subjects with some organ failure	From study start to day 28
Proportion of patients who have modified their oxygen therapy requirements between treatment assessment visit and baseline	Proportion of patients who have modified their oxygen therapy requirements between treatment assessment visit and baseline	From study start to day 28
Proportion of subjects with pathological angioTAC	Proportion of subjects with pathological angioTAC at day 10 +/-1	At day 10 +/-1
Proportion of subjects with improvement in chest radiography	Proportion of subjects with improvement in chest radiography	At day 10 +/-1
Proportion and median hospital discharge between patients in both groups.	Proportion and median hospital discharge between patients in both groups.	From study start to day 28
Titration score	Titration score	From study start to day 28
Ferritin score	Ferritin score	From study start to day 28
D-dimer modification score	D-dimer modification score	From study start to day 28
Adverse events (total and serious).	Adverse events (total and serious)	From study start to day 28
Related adverse events (total and serious).	Related adverse events (total and serious).	From study start to day 28
Clinically relevant major and non major hemorrhages.	Clinically relevant major and non major hemorrhages.	From study start to day 28

Collaborators and Investigators

• Sponsor: Fundación de investigación HM
• Collaborators: Syntax for Science, S.L
• Investigators: Study Director: Antonio Cubillo, MD, Director

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): June 4, 2020
• Primary Completion (Actual): June 8, 2021
• Study Completion (Actual): June 8, 2021

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): June 7, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: covid-19; d-dimer; immunothrombosis
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Bemiparin
• Other Study ID Numbers: BEMICOVID-19; 2020-001548-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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