NCT04600141

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
308

participants targeted

Target at P25-P50 for phase_3 covid19

Timeline
Completed

Started Nov 2020

Typical duration for phase_3 covid19

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 22, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 23, 2020

Completed
18 days until next milestone

Study Start

First participant enrolled

November 10, 2020

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 20, 2021

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2021

Completed
Last Updated

March 18, 2022

Status Verified

March 1, 2022

Enrollment Period

11 months

First QC Date

October 22, 2020

Last Update Submit

March 17, 2022

Conditions

Covid19

Keywords

COVID-19HeparinTocilizumab

Outcome Measures

Primary Outcomes (1)

  • 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: 1. Not hospitalized, with no limitations on activities; 2. Not hospitalized, but limited to activities; 3. Hospitalized, with no need for supplemental oxygen; 4. Hospitalized, needing supplemental oxygen; 5. Hospitalized, requiring high flow oxygen therapy, non-invasive mechanical ventilation or both; 6. Hospitalized, requiring ECMO, invasive mechanical ventilation or both; 7. Death.

    30 days

Secondary Outcomes (7)

  • Hospital and ICU length of stay;

    30 days

  • Duration of invasive mechanical ventilation

    30 days

  • Duration of vasopressor use

    30 days

  • Renal failure by AKIN criteria

    30 days

  • Incidence of cardiovascular complications

    30 days

  • +2 more secondary outcomes

Study Arms (4)

Group 1 - Therapeutic anticoagulation

ACTIVE COMPARATOR

* (I) intravenous UFH started at a dose of 18 IU/kg/h, adjusted according to a nomogram to achieve a TTPa of 1.5 to 2.0 times the reference value; OR * (II) subcutaneous LMWH - enoxaparin 1 mg / kg per dose every 12 hours.

Drug: Heparin - Therapeutic dosage

Group 2 - Prophylactic anticoagulation

ACTIVE COMPARATOR

* (I) subcutaneous UFH 5,000 IU every 8 hours; OR * (II) subcutaneous LMWH - enoxaparin 40 mg daily.

Drug: Heparin - Prophylactic dosage

Group 3 - Therapeutic anticoagulation with tocilizumab

EXPERIMENTAL

* (I) Intravenous UFH initiated at a dose of 18 IU / kg / h, adjusted according to a nomogram to achieve a TTPa of 1.5 to 2.0 times the reference value associated with 8 mg / kg / tocilizumab infusion / intravenous dose in a single dose; OR * Subcutaneous LMWH - enoxaparin 1 mg / kg per dose every 12 hours associated with an infusion of tocilizumab 8 mg / kg / dose in a single dose.

Drug: TocilizumabDrug: Heparin - Therapeutic dosage

Group 4 - Prophylactic anticoagulation with tocilizumab

EXPERIMENTAL

* (I) subcutaneous UFH 5,000 IU every 8 hours associated with an infusion of tocilizumab 8 mg / kg / intravenous dose in a single dose; OR * (II) subcutaneous LMWH - enoxaparin 40 mg daily associated with an infusion of tocilizumab 8 mg / kg / intravenous dose in a single dose.

Drug: TocilizumabDrug: Heparin - Prophylactic dosage

Interventions

TocilizumabDRUG

Tocilizumab infusion 8mg/kg/dose - Intravenous single dose.

Group 3 - Therapeutic anticoagulation with tocilizumabGroup 4 - Prophylactic anticoagulation with tocilizumab
Heparin - Therapeutic dosageDRUG

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

Group 1 - Therapeutic anticoagulationGroup 3 - Therapeutic anticoagulation with tocilizumab
Heparin - Prophylactic dosageDRUG

Subcutaneous Non-Fractional Heparine 5000U every 8 hours OR Subcutaneous Low Molecular Weight (LMWH) 40mg/day.

Group 2 - Prophylactic anticoagulationGroup 4 - Prophylactic anticoagulation with tocilizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years;
  • Informed consent form signed by the patient or guardian or by audio with the guardian;
  • Need for ≥ 4 L of supplemental oxygen to maintain peripheral oxygen saturation equal to or greater than 93% or need for invasive mechanical ventilation.

You may not qualify if:

  • 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;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Fundação São Francisco Xavier

Ipatinga, Minas Gerais, Brazil

Location

UNIMED Varginha

Varginha, Minas Gerais, Brazil

Location

Universidade Federal de Sergipe

Aracaju, Sergipe, Brazil

Location

MeSH Terms

Conditions

COVID-19

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Ludhmila A Hajjar, MD, PhD

    InCor - University of Sao Paulo Medical School

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

October 22, 2020

First Posted

October 23, 2020

Study Start

November 10, 2020

Primary Completion

October 20, 2021

Study Completion

December 31, 2021

Last Updated

March 18, 2022

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will not share

Locations

BR(3)