Multi-site Adaptive Trials for COVID-19

• Status: Completed
• Trial end date: 2020-09-07
• Target enrollment: 0
• Participant gender: All

Summary

The overall objective of the study is to evaluate the clinical efficacy of COVID-19 treatments consisting of standard of care (SOC), vs SOC with high dose famotidine in patients hospitalized and meeting radiologic criteria for COVID-19 disease. SOC for the treatment for COVID-19 has evolved since the initial conceptualization of this protocol and early recruitment of patients. Initially SOC included hydroxychloroquine and has progressed to include Remdesivir. This protocol is amended to allow the SOC to reflect the prevailing treatment for COVID-19. We will compare clinical outcomes associated with SOC and the addition of high-dose intravascular famotidine. The trial is designed to enroll at least 471 COVID-19 patients hospitalized with moderate to severe disease into each of the two treatment arms, with a total enrollment target of at least 942 patients. This trial has been designed and powered to support up to three interim analyses that will enable prompt assessment of benefits and risks of the two treatment groups while maintaining the rigorous gold standard of a randomized double blind clinical trial structure. Trial design has been guided by practical consideration of the current clinical context involving rapidly escalating demands on hospital staff and resources, and incorporates a minimalist approach employing existing laboratory information management systems and a clinically relevant binary primary outcome of 30-day endpoint of death or survival.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwell Health
• Treatments: Famotidine

Criteria

Inclusion Criteria:

1. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.

2. Understands and agrees to comply with planned study procedures.

3. Male or non-pregnant female adult ≥18 years of age at time of enrollment.

4. Subject consents to randomization within 36 hours of hospital admission.

5. Has radiographic confirmed COVID-19 disease < 72 hours prior to randomization.

6. Illness of any duration, and at least one of the following:

• Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

• Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, OR

• Requiring mechanical ventilation and/or supplemental oxygen.

7. Subjects do not require laboratory confirmation of the corona virus SARS-CoV-2 to determine eligibility

8. Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study (acceptable methods will be determined by the site).

Exclusion Criteria:

1. Mild COVID-19 disease (minor clinical symptoms, imaging does not show signs of lung inflammation)

2. Recent history of or any in-hospital exposure to investigational medications targeting COVID-19, or concurrent participation in a clinical trial targeting COVID-19

3. ALT/AST > 5 times the upper limit of normal.

4. Moderate renal insufficiency (creatinine clearance 30-50 mL/min) OR Stage 4 severe chronic kidney disease OR requiring dialysis (i.e. creatinine clearance <30 mL/min)

5. History of or evidence of QT prolongation on ECG examination

6. History of psoriasis or porphyria

7. Absolute neutrophil count (ANC) is < 2000 mm3

8. Pregnancy

9. History of hepatic disease, Hepatitis C infection, or alcoholism

10. History of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency

11. Concomitant use of the following medications: atazanavir, dasatinib, neratinib, ozanimod, pazopanib, rilpivirine, siponimod, and/or tizanidine.

12. Anticipated transfer to another hospital which is not a study site within 72 hours.

13. Allergy to any study medication

14. Known to be immunocompromised by disease or treatment for existing disease