Hemostasis in COVID-19: an Adaptive Clinical Trial

University of Sao Paulo General Hospital

Status and phase: Unknown; Phase 2

Conditions: COVID-19

Treatments: Drug: acetylsalicylic acid; Drug: Unfractionated heparin nebulized

Study type: Interventional

Funder types: Other

Identifiers

NCT04466670

33788820.9.0000.0068

Details and patient eligibility

About

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.

Enrollment: 379 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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379 participants in 4 patient groups, including a placebo group

phase 1

No Intervention group

Description:

Observational arm

phase 2A

Experimental group

Description:

Acetylsalicylic acid

Treatment:

Drug: acetylsalicylic acid

phase 2B

Experimental group

Description:

inhaled unfractionated heparin

Treatment:

Drug: Unfractionated heparin nebulized

Placebo

Placebo Comparator group

Description:

Placebo arm for Phase 2A

Treatment:

Drug: acetylsalicylic acid