Multi-site Adaptive Trials for COVID-19

NCT04370262 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 20-0268
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

COVID-19

Keywords

COVID-19; Coronavirus; Famotidine

Outcome Measures

Primary Outcomes (1)

• Mortality

  Mortality status

  30 days post hospitalization

Secondary Outcomes (7)

• Virologic response to study treatment detected in blood

  Day 30 relative to admission Day 0

• Virologic clearance in nasal swab and/or lower respiratory secretions

  Day 6 and Day 30

• Clinical Severity

  Measured on study Days 3, 5, 8, 11, 15 and 30.

• Clinical Severity

  Measured on study Days 3, 5, 8, 11, 15 and 30.

• Clinical Severity

  Measured on study Days 3, 5, 8, 11, 15 and 30.

Other Outcomes (1)

• Incidence of New Onset Lymphopenia

  Through study completion, average of 30 days

Study Arms (2)

SOC/Famotidine

ACTIVE COMPARATOR

Subjects in this study arm will receive a combination of Standard of Care (SOC) treatment and intravenous famotidine. Famotidine Injection, 10mg/mL mixed with Normal Saline is given intravenously at 120mg (30% of 400 mg oral dose). The total daily dose proposed is 360mg/day famotidine IV for a maximum of 14 days, or hospital discharge, whichever comes first. SOC will be administered as per the current clinical protocol for COVID-19.

Drug: SOC + Intravenous Famotidine

SOC/Placebo

PLACEBO COMPARATOR

Subjects in this arm will receive the current Standard of Care treatment for COVID-19; plus placebo infusion three times daily.

Drug: SOC + Placebo

Interventions

SOC + Intravenous Famotidine DRUG

Standard of Care treatment plus IV famotidine

SOC/Famotidine

SOC + Placebo DRUG

Standard of Care treatment plus IV placebo

SOC/Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
• Understands and agrees to comply with planned study procedures.
• Male or non-pregnant female adult ≥18 years of age at time of enrollment.
• Subject consents to randomization within 36 hours of hospital admission.
• Has radiographic confirmed COVID-19 disease \< 72 hours prior to randomization.
• 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.
• Subjects do not require laboratory confirmation of the corona virus SARS-CoV-2 to determine eligibility
• 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).

You may not qualify if:

• Mild COVID-19 disease (minor clinical symptoms, imaging does not show signs of lung inflammation)
• Recent history of or any in-hospital exposure to investigational medications targeting COVID-19, or concurrent participation in a clinical trial targeting COVID-19
• ALT/AST \> 5 times the upper limit of normal.
• 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)
• History of or evidence of QT prolongation on ECG examination
• History of psoriasis or porphyria
• Absolute neutrophil count (ANC) is \< 2000 mm3
• Pregnancy
• History of hepatic disease, Hepatitis C infection, or alcoholism
• History of G-6-PD (glucose-6-phosphate dehydrogenase) deficiency
• Concomitant use of the following medications: atazanavir, dasatinib, neratinib, ozanimod, pazopanib, rilpivirine, siponimod, and/or tizanidine.
• Anticipated transfer to another hospital which is not a study site within 72 hours.
• Allergy to any study medication
• Known to be immunocompromised by disease or treatment for existing disease

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (5)

Southside Hospital

Bay Shore, New York, 11706, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Northern Westchester Hospital

Mount Kisco, New York, 10549, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

Long Island Jewish Medical Center

Queens, New York, 11040, United States

Location

Related Publications (11)

• Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, Li Y, Hu Z, Zhong W, Wang M. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020 Mar 18;6:16. doi: 10.1038/s41421-020-0156-0. eCollection 2020. No abstract available.

  PMID: 32194981 BACKGROUND

• Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016 Jun;123(6):1386-94. doi: 10.1016/j.ophtha.2016.01.058. Epub 2016 Mar 16.

  PMID: 26992838 BACKGROUND

• Amrane S, Tissot-Dupont H, Doudier B, Eldin C, Hocquart M, Mailhe M, Dudouet P, Ormieres E, Ailhaud L, Parola P, Lagier JC, Brouqui P, Zandotti C, Ninove L, Luciani L, Boschi C, La Scola B, Raoult D, Million M, Colson P, Gautret P. Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot. Travel Med Infect Dis. 2020 Jul-Aug;36:101632. doi: 10.1016/j.tmaid.2020.101632. Epub 2020 Mar 20.

  PMID: 32205269 BACKGROUND

• Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum. 1993 Oct;23(2 Suppl 1):82-91. doi: 10.1016/s0049-0172(10)80012-5.

  PMID: 8278823 BACKGROUND

• Yao Y, Tian Y, Zhou J, Ma X, Yang M, Wang S. Epidemiological characteristics of SARS-CoV-2 infections in Shaanxi, China by 8 February 2020. Eur Respir J. 2020 Apr 23;55(4):2000310. doi: 10.1183/13993003.00310-2020. Print 2020 Apr.

  PMID: 32139462 BACKGROUND

• Wang L, Gao YH, Lou LL, Zhang GJ. The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China. Eur Respir J. 2020 Apr 23;55(4):2000398. doi: 10.1183/13993003.00398-2020. Print 2020 Apr.

  PMID: 32139464 BACKGROUND

• Geleris J, Sun Y, Platt J, Zucker J, Baldwin M, Hripcsak G, Labella A, Manson DK, Kubin C, Barr RG, Sobieszczyk ME, Schluger NW. Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med. 2020 Jun 18;382(25):2411-2418. doi: 10.1056/NEJMoa2012410. Epub 2020 May 7.

  PMID: 32379955 BACKGROUND

• Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, Ambati J. Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19. Med. 2020 Dec 18;1(1):114-127.e3. doi: 10.1016/j.medj.2020.06.001. Epub 2020 Jun 5.

  PMID: 32838355 BACKGROUND

• Freedberg DE, Conigliaro J, Wang TC, Tracey KJ, Callahan MV, Abrams JA; Famotidine Research Group. Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. Gastroenterology. 2020 Sep;159(3):1129-1131.e3. doi: 10.1053/j.gastro.2020.05.053. Epub 2020 May 22. No abstract available.

  PMID: 32446698 BACKGROUND

• Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, Fu S, Gao L, Cheng Z, Lu Q, Hu Y, Luo G, Wang K, Lu Y, Li H, Wang S, Ruan S, Yang C, Mei C, Wang Y, Ding D, Wu F, Tang X, Ye X, Ye Y, Liu B, Yang J, Yin W, Wang A, Fan G, Zhou F, Liu Z, Gu X, Xu J, Shang L, Zhang Y, Cao L, Guo T, Wan Y, Qin H, Jiang Y, Jaki T, Hayden FG, Horby PW, Cao B, Wang C. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-1578. doi: 10.1016/S0140-6736(20)31022-9. Epub 2020 Apr 29.

  PMID: 32423584 BACKGROUND

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joseph Conigliaro, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chairperson, Medicine, General Internal Medicine

Model Details: Randomized, Double-Blind Comparative Trial

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 30, 2020
• Study Start: April 7, 2020
• Primary Completion: September 7, 2020
• Study Completion: September 7, 2020
• Last Updated: December 11, 2020

Record last verified: 2020-12

Locations

US (5)