Trial of Famotidine & N-Acetyl Cysteine for Outpatients With COVID-19

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to assess the safety and toxicity profile of the combination of famotidine and oral n-acetyl cysteine in adult outpatients with newly diagnosed SARS-CoV-2 infection.

Detailed Description
-----------------
This is a phase I trial enrolling subjects with newly diagnosed SARS-CoV-2 infection who do not require hospitalization. Exclusion criteria have been written to exclude patients who would be expected to have increased risk from either medication alone. Subjects will be assigned a dose combination of famotidine and n-acetyl cysteine. In addition to assessing the safety and toxicities profiles of the combination of drugs we will be measuring certain endpoints to assess possible efficacy. These endpoint include the following: rates of hospitalization; time to complete remission of symptoms, e.g, fever, respiratory symptoms, etc.; severity of symptoms with validated survey instruments; cytokine values in serum and urine; and markers of inflammation and oxidative stress.

Official Title
-----------------
A Phase I Clinical Trial of the Combination of Famotidine (FAM) and Oral N-Acetyl Cysteine (NAC) Open Label for Outpatient Treatment of Subjects With Newly Diagnosed SARS-CoV-2 Infection

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: Famotidine
* Drug: N-Acetyl cysteine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 performance of a SARS-CoV-2 test within 1 day of enrollment, N.B., must be positive to proceed to treatment phase of the trial Exclusion Criteria: All patients under 18 Known allergy to N-Acetyl Cysteine Known allergy to famotidine or other H2-receptor antagonists Pregnant or Nursing Mothers Laboratory Evidence or History of Renal Impairment (eGFR < 30 mL/min/1.73 m2) Taking H2-receptor antagonists, hydroxychloroquine or chloroquine. Patient has been admitted to the hospital prior to study enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose N-Acetyl Cysteine Alone<br>N-Acetyl Cysteine 600 mg three times daily | Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Medium Dose N-Acetyl Cysteine<br>N-Acetyl Cysteine 1,200 mg three times daily | Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Low Dose N-Acetyl Cysteine and Low Dose Famotidine<br>N-Acetyl Cysteine 600 mg three times daily Famotidine 20 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: High Dose N-Acetyl Cysteine Alone<br>N-Acetyl Cysteine 1,800 mg three times daily | Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Medium Dose N-Acetyl Cysteine and Low Dose Famotidine<br>N-Acetyl Cysteine 1,200 mg three times daily Famotidine 20 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Low Dose N-Acetyl Cysteine and Medium Dose Famotidine<br>N-Acetyl Cysteine 600 mg three times daily Famotidine 40 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: High Dose N-Acetyl Cysteine and Low Dose Famotidine<br>N-Acetyl Cysteine 1,800 mg three times daily Famotidine 20 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Medium Dose N-Acetyl Cysteine and Medium Dose Famotidine<br>N-Acetyl Cysteine 1,200 mg three times daily Famotidine 40 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Low Dose N-Acetyl Cysteine and High Dose Famotidine<br>N-Acetyl Cysteine 600 mg three times daily Famotidine 80 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: High Dose N-Acetyl Cysteine and Medium Dose Famotidine<br>N-Acetyl Cysteine 1,800 mg three times daily Famotidine 40 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: Medium Dose N-Acetyl Cysteine and High Dose Famotidine<br>N-Acetyl Cysteine 1,200 mg three times daily Famotidine 80 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|
| Experimental: High Dose N-Acetyl Cysteine and High Dose Famotidine<br>N-Acetyl Cysteine 1,800 mg three times daily Famotidine 80 mg three times daily | Drug: Famotidine<br>* Oral Famotidine<br>* Other names: Pepcid AC;Drug: N-Acetyl cysteine<br>* Oral N-Acetyl Cysteine<br>* Other names: NAC;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 | Data will be collected and entered into Case Report Form in local REDCap sever to include MedDRA Code, Grade and all other data required by NIH per Memorandum, Guidance for Collection of Adverse Events Related to COVID-19 Infection dated on 25 March 2020. All data will be reported per this memorandum and in accordance with all applicable Institutional Review Board and FDA requirements. | 0 to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Hospitalization | Number of participants hospitalized | 0 to 30 days | 
| Time to Symptom Resolution | Days to resolution of symptoms of infection. | 0 to 30 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
outpatient, famotidine, n-acetyl cysteine