Leidos-Enabled Adaptive Protocol for Clinical Trials (LEAP-CT) in Hospitalized Patients With COVID-19 (Addendum 1)

Exclusion Criteria

• •Participants are excluded from the study if any of the following criteria apply:
• •Pregnant or breastfeeding
• •History of HIV
• •Ongoing treatment that cannot be temporarily discontinued during the study: anti-inflammatory treatment (nonsteroidal anti-inflammatory drugs \[NSAIDS\]);corticosteroids; antimalarials; antiarrhythmics; tricyclic antidepressants; natalizumab; quinolones; macrolides; and agalsidase alfa and beta
• •1. drugs dependent on gastric pH for absorption, e.g., dasatinib, delavirdine, mesylate, cefditoren, and fosamprenavir;
• •2. tizanidine (CYP1A2) substrate;
• •3. drugs that interfere with hemostasis (e.g., warfarin, aspirin, selective serotonin reuptake inhibitors \[SSRIs\]/serotonin norepinephrine reuptake inhibitors \[SNRIs\]);
• •4. angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), or beta-blockers;
• •5. diuretics;
• •6. digoxin
• •Ongoing famotidine, celecoxib, or other COVID-19 clinical investigational treatment(s) within the past 30 days or current participation in another investigational clinical trial
• •History of immunosuppression
• •History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
• •Rejection of participation at the discretion of the Principal Investigator or Sponsor
• •Any contraindication for famotidine or celecoxib treatment:
• •a. Famotidine or celecoxib hypersensitivity; b. Retinopathy, visual field or visual acuity disturbances; c. History of cardiovascular disease, such as congestive heart failure, QT prolongation, bradycardia (\<50 bpm), ventricular tachycardia, other arrhythmias, as determined at screening electrocardiogram (ECG) or medical history; d. Potassium \<3 mEq/L (milliequivalent/liter) as determined at Visit 1; e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5 upper normal limit, as determined at Visit 1; f. Previous myocardial infarction; e. Myasthenia gravis; h. Psoriasis or porphyria; i. Glomerular clearance, 60 mL/min; j. Previous history of severe hypoglycemia; k. Known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history or experience with other CYP2C9 substrates, such as warfarin and phenytoin; l. Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C.