Hemostasis in COVID-19: an Adaptive Clinical Trial

Phase 2

• Conditions: COVID-19
• Interventions: Drug: acetylsalicylic acid; Drug: Unfractionated heparin nebulized

• Registration Number: NCT04466670
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

Hypercoagulability has been demonstrated in COVID-19, leading to respiratory distress and increased mortality. This is an adaptive clinical trial to compare the efficacy and safety of two experimental strategies in patients with COVID-19: ASA or inhaled UFH associated with standard VTE prophylaxis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-08
• Study First Submitted QC: 2020-07-08
• Study First Posted: 2020-07-10
• Study Start: 2020-07-11
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-04
• Last Update Posted: 2021-06-09
• Primary Completion: 2021-12-30
• Study Completion: 2022-05-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 379

Inclusion Criteria

• Adult ≥18 years of age at time of enrollment

• Subjects with a positive COVID-19 diagnosis by RT-PCR or serologic testing

• Subject (or legally authorized representative) must be willing, understanding and able to provide written informed consent.

• Only at phase 2:

  • onset of symptoms must not exceed 4 weeks
  • ICU patients
  • PaO2 to FiO2 ratio < 200

Exclusion Criteria

1. General

   • Indications for therapeutic anticoagulation
   • History of chronic lung disease oxygen dependent
   • Pregnancy
   • Death considered imminent and inevitable within 24 hours
   • Patients under exclusive palliative care
   • Participation in another trial of investigational drug
   • Body weight < 40 Kg
   • Total bilirubin > 20 mg/dL
   • Severe active bleeding
   • Persistent GI bleeding
   • Known allergy to UFH or LMWH
   • History of heparin-induced thrombocytopenia (HIT) within the past 6 months

2. Exclusion criteria at phase 1

   • Platelet count < 25,000/mm3
   • Bacterial endocarditis

3. Exclusion criteria at phase 2

   • Platelet count < 50,000/mm3
   • History of surgery in the last 30 days
   • Intervention A: allergy to ASA and long-term use of antiplatelet drug
   • Intervention B: inhaled nitric oxide use

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	acetylsalicylic acid	Placebo arm for Phase 2A
phase 2A	acetylsalicylic acid	Acetylsalicylic acid
phase 2B	Unfractionated heparin nebulized	inhaled unfractionated heparin

Primary Outcome Measures

Name	Time	Method
Hospital discharge - alive / death	30 days	Number of COVID-19 positive patients who are alive within 30 days of symptoms onset

Secondary Outcome Measures

Name	Time	Method
Length of renal replacement therapy free days	30 days	Comparison of length of renal replacement therapy free days between each treatment arm
Length of mechanical ventilation free days	30 days	Comparison of length of mechanical ventilation free days between each treatment arm
Number of documented venous thromboembolism or arterial thrombosis	3 months	Comparison of number of thrombosis events between each treatment arm.

Trial Locations

Locations (1)

Vanderson Rocha; 🇧🇷 Sao Paulo, Brazil