Clinical trial NCT04600141: Clinical Efficacy of Heparin and Tocilizumab in Patients With Severe COVID-19 Infection
Official title: Clinical Efficacy of Heparin and Tocilizumab in Patients With Severe COVID-19 Infection: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid19
Keywords: COVID-19
Heparin
Tocilizumab
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Conselho Nacional de Desenvolvimento Científico e Tecnológico
First posted: 2020-10-23
Enrollment: 308
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with clinical improvement
timeFrame: 30 days
Secondary outcomes:
measure: Hospital and ICU length of stay;
timeFrame: 30 days
measure: Duration of invasive mechanical ventilation
timeFrame: 30 days
measure: Duration of vasopressor use
timeFrame: 30 days
measure: Renal failure by AKIN criteria
timeFrame: 30 days
measure: Incidence of cardiovascular complications
timeFrame: 30 days
measure: Incidence of venous thromboembolism
timeFrame: 30 days
measure: Mortality
timeFrame: 30, 60 and 90 days
Other outcomes:
Locations:
city: Ipatinga
country: Brazil
facility: Fundação São Francisco Xavier
state: Minas Gerais
city: Varginha
country: Brazil
facility: UNIMED Varginha
state: Minas Gerais
city: Aracaju
country: Brazil
facility: Universidade Federal de Sergipe
state: Sergipe
Study officials:
affiliation: InCor - University of Sao Paulo Medical School
name: Ludhmila A Hajjar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: