Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19

Sponsor

Northwell Health (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04724720

Collaborator

Cold Spring Harbor Laboratory (Other)

Enrollment

Location

Arms

16.4

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall objective of this study is to evaluate the clinical efficacy of oral famotidine in symptomatic non-hospitalized patients with confirmed COVID-19. This study is expected to enroll up to 84 patients with mild to moderate symptoms divided into each of the two study arms. Clinical outcomes of the two treatment arms will be compared. This study will be conducted virtually/remotely.

Condition or Disease	Intervention/Treatment	Phase
Covid-19	Drug: Famotidine Drug: Placebo	Phase 2

Detailed Description

The outbreak of coronavirus disease 2019 (COVID 19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was first reported in Wuhan, China, in 31 December 2019 and was declared as a global health emergency on 30 January 2020. Currently, there are no definitive vaccine, therapeutic antibody, or antiviral drug countermeasures currently authorized by the FDA for prevention or treatment of mild to moderate COVID-19 disease.

Famotidine is a histamine-2 receptor antagonist, widely available over-the-counter and at low cost, does not interact with other medications and is safely used for suppression of gastric acid production. This makes it a candidate medication for an ambulatory setting to alleviate the symptoms and shorten the symptomatic period in this population. In a case series of 10 patients with COVID-19 who self-medicated with oral famotidine, significant improvement of symptoms was associated with famotidine use after 24-48 hours. These effects were noted in patients who mostly took doses of 80mg three times daily suggesting that famotidine's action is either through its main known high affinity target, the histamine type 2 receptor or through combined inhibition of histamine receptors. Famotidine may work through reduction of H2R signaling on monocytes with a resulting reduction of cytokine release.

The working hypothesis is that famotidine will be superior to placebo in reducing disease related symptoms in non-hospitalized COVID-19 patients with mild or moderate disease. Patients will be monitored for the duration of the study, as well as be asked to record the severity of their symptoms through a daily questionnaire. Current standard of care (SOC) for patients with mild to moderate COVID-19 in the outpatient setting is to assess risk for severe disease and determine the need for an in-person visit, thromboprophylaxis and adjustment of home medication regimen. If the SOC for COVID-19 patients in the outpatient setting changes during the course of the study, a request will be submitted to modify sections of the protocol.

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, Double-Blind Comparative Placebo Controlled TrialRandomized, Double-Blind Comparative Placebo Controlled Trial

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Comparative Trial of the Safety and Efficacy of Famotidine vs Placebo for the Treatment of Non-Hospitalized Symptomatic Adults With COVID-19

Actual Study Start Date :

Jan 19, 2021

Actual Primary Completion Date :

May 3, 2021

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Famotidine Participants in this study arm will receive standard of care and prescribed famotidine at 80mg TID for a maximum of 14 days, or until hospital admission.	Drug: Famotidine Standard or care treatment plus prescribed famotidine
Placebo Comparator: Placebo Participants in this study arm will receive standard of care and placebo for a maximum of 14 days.	Drug: Placebo Standard of care treatment plus placebo

Arm

Intervention/Treatment

Active Comparator: Famotidine

Participants in this study arm will receive standard of care and prescribed famotidine at 80mg TID for a maximum of 14 days, or until hospital admission.

Drug: Famotidine

Standard or care treatment plus prescribed famotidine

Placebo Comparator: Placebo

Participants in this study arm will receive standard of care and placebo for a maximum of 14 days.

Drug: Placebo

Standard of care treatment plus placebo

Outcome Measures

Primary Outcome Measures

Cumulative incidence of symptom resolution [Day 28]
Measured by the cumulative incidence of symptom resolution using the "COVID-19 Symptom Score" derived from the answers to a questionnaire based on the NIH endorsed guidelines and the recent FDA guidelines for studying COVID-19 in an outpatient setting. A shorter version has been utilized as a scoring system in the case series of famotidine use in non-hospitalized patients with COVID-19.

Secondary Outcome Measures

Rate of symptom resolution [Day 28]
Assessed by modelling the resolution of cumulative symptoms over time
Cumulative incidence of symptom resolution [Day 60]
Assessed using the "COVID-19 Symptom Score"
Relative change of symptoms [Day 7]
Assessed using the "COVID-19 Symptom Score"
Assessment of Serious Adverse Events [Day 60]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Clinical improvement [Day 28]
Assessed using the 9-point ordinal scale recommended by the WHO for trials enrolling patients with COVID-19.
Improvement in peripheral oxygen saturation [Day 7]
Measured by pulse oximetry in % oxygen saturation.
Mortality [Day 28]
Assessed by counting mortality in each arm
Comparative proportions of hospitalized patients [Day 0-28]
Measured by the proportions of patients having been hospitalized by Day 28.
Change in CRP [Day 7, 14, and 28.]
Measured by CRP [mg/L]
Change in procalcitonin [Day 7, 14, and 28.]
procalcitonin [microg/L]
Change in ferritin [Day 7, 14, and 28.]
ferritin [microg/L]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Adult ≥18 years of age at time of enrollment.
Subject consents to randomization.
Subject has confirmed COVID-19 disease < 72 hours prior to randomization.
Subject has been experiencing symptoms for >1 day but ≤7 days.
Able to use an electronic tablet and Bluetooth devices.
Subject has mild to moderate COVID-19 which is defined as (equivalent to 1, 2 on the

WHO scale):

Patient does not require immediate admission to the hospital within 24 hrs of initial assessment
Patient does not require supplemental oxygen due to COVID-19
Patient has a score of 2 ("moderate") in at least 3 of the symptoms in the COVID- 19 symptom score

Exclusion Criteria:

Any exposure to investigational medications targeting COVID-19 during the present disease. These include recently approves antibodies (passive immunization) for treatment of COVID-19.
Use of famotidine within the last 30 days for any indication, e.g. medicating gastric ulcer or recent off label use for COVID-19.
Severe COVID-19 disease at time of enrollment requiring admission to hospital.
History of Stage 3 severe chronic kidney disease, i.e. eGFR of < 60ml/min.
Allergy to famotidine or non-medical ingredients of the study tablet.
Known to be immunocompromised by treatment for existing disease due to the immunomodulatory effects of famotidine and therefore possible effects on the pre- existing disease or the immunosuppressive therapy.
Patients currently using tizanidine.
Documented deficiency of any of the following minerals: Al, Cu, Mn, Fe and Zn.
Inability to perform the tasks required for the patient reported outcome measure recordings, including but not restricted to limited language proficiency.
Have symptoms of dysphagia or inability to swallow size #000 capsules.