Clinical Efficacy of Heparin and Tocilizumab in Patients With Severe COVID-19 Infection

Covid19 Clinical Trial

— HEPMAB  

Official title:

Clinical Efficacy of Heparin and Tocilizumab in Patients With Severe COVID-19 Infection: a Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04600141
• Other study ID #: HEPMAB
• Status: Completed
• Phase: Phase 3
• Start date: November 10, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: March 2022
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The COVID-19 infection primarily manifests itself as a respiratory tract infection, although new evidence indicates that this disease has systemic involvement involving multiple systems including the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic and immune systems. Recent studies have shown that in its pathophysiology, inflammation and thrombogenesis predominate, especially in the severe forms of COVID-19. Thus, the investigators hypothesized that the use of heparin and tocilizumab could potencially reduce inflammation and thrombogenesis in patients with severe COVID-19 infection, improving patients outcomes and survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 308
• Est. completion date: December 31, 2021
• Est. primary completion date: October 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years;
• Informed consent form signed by the patient or guardian or by audio with the guardian;
• Positive result for COVID-19 in PCR (polymerase chain reaction) in nasopharyngeal swab or tracheal secretion up to 10 days before the inclusion and radiological evidence of COVID-19, by chest radiography or chest computed tomography;
• Need for = 4 L of supplemental oxygen to maintain peripheral oxygen saturation equal to or greater than 93% or need for invasive mechanical ventilation.

Exclusion Criteria:

• Risk of bleeding:
• Clinical: active bleeding, major surgery in the last 30 days, gastrointestinal bleeding within 30 days;
• Laboratory: platelet count <50,000, INR> 2 or APTT> 50s;
• Known or suspected adverse reaction to UFH, including heparin-induced thrombocytopenia (TIH);
• Adverse reaction or allergy to tocilizumab;
• Use of any of the following treatments: UFH to treat a thrombotic event within 12 hours before inclusion; HPBM in therapeutic dose within 12 hours before inclusion; warfarin (if used 7 days before and if INR greater than 2; thrombolytic therapy within 3 days before; and use of glycoprotein IIb / IIIa inhibitors within the previous 7 days;
• Pregnant or lactating;
• Absolute indication of anticoagulation due to atrial fibrillation or diagnosed thromboembolic event;
• Refusal by family members and / or patient;
• Active tuberculosis;
• Bacterial infection confirmed by culture;
• Neutropenia (<1000 neutrophils / mm3);
• Use of another immunosuppressive therapy that is not a corticosteroid;
• Septic shock.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• Tocilizumab
Tocilizumab infusion 8mg/kg/dose - Intravenous single dose.
• Heparin - Therapeutic dosage
Intravenous Non-Fractional Heparine (HNF) starting at 18UI/kg/h adjusted according to a nomogram to achieve an Activated Partial Thromboplastin Time (ATTP) from 1.5 To 2.0 times the reference Value; or Low Molecular Weight Heparin (LMWH) subcutaneous dosage of 1mg/kg per dose every 12 hours
• Heparin - Prophylactic dosage
Subcutaneous Non-Fractional Heparine 5000U every 8 hours OR Subcutaneous Low Molecular Weight (LMWH) 40mg/day.

Locations

Country	Name	City	State
Brazil	Universidade Federal de Sergipe	Aracaju	Sergipe
Brazil	Fundação São Francisco Xavier	Ipatinga	Minas Gerais
Brazil	UNIMED Varginha	Varginha	Minas Gerais

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Conselho Nacional de Desenvolvimento Científico e Tecnológico

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with clinical improvement	Proportion of patients with clinical improvement in 30 days, defined by hospital discharge or a reduction of at least 2 points compared to baseline on the ordinal scale recommended by the World Health Organization: Not hospitalized, with no limitations on activities; Not hospitalized, but limited to activities; Hospitalized, with no need for supplemental oxygen; Hospitalized, needing supplemental oxygen; Hospitalized, requiring high flow oxygen therapy, non-invasive mechanical ventilation or both; Hospitalized, requiring ECMO, invasive mechanical ventilation or both; Death.	30 days
Secondary	Hospital and ICU length of stay;	Number of days in hospital and ICU	30 days
Secondary	Duration of invasive mechanical ventilation	Time requiring invasive mechanical ventilation	30 days
Secondary	Duration of vasopressor use	Time of use of vasopressors	30 days
Secondary	Renal failure by AKIN criteria	Renal failure by AKIN criteria in 30 days	30 days
Secondary	Incidence of cardiovascular complications	Myocardial injury; Acute myocardial infarction; Cardiogenic shock; arrhythmias; Myocarditis; Pericarditis; Ventricular dysfunction.	30 days
Secondary	Incidence of venous thromboembolism	Deep vein thrombosis and pulmonary embolism	30 days
Secondary	Mortality	Mortality rate	30, 60 and 90 days