Ketotifen and Indomethacin Combination Treatment Clinical Trial for COVID-19

NCT05007522 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: Pro00108924
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of ketotifen and indomethacin taken together to improve symptoms related with COVID-19. Ketotifen and indomethacin are medications approved by the Food and Drug Administration (FDA) to treat diseases other than COVID-19. Their use in this study is investigational, meaning they have not been approved by the FDA to treat COVID-19.

Conditions

COVID-19 Respiratory Infection

Outcome Measures

Primary Outcomes (1)

• UCSD Shortness of Breath Questionnaire

  24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living.

  Study Day 14

Secondary Outcomes (43)

• Development of severe disease

  28 days

• Development of severe disease

  84 days

• Development of severe disease

  14 days

• Proportion and number of medically attended visits related to COVID-19

  28 days

• Proportion and number of medically attended visits related to COVID-19

  84 days

Study Arms (2)

Study Drug

EXPERIMENTAL

Ketotifen 2 mg administered in tablet form twice a day (every 12 hr). Indomethacin sustained-release (SR) 75 mg, twice a day (every 12 hr). Patients will be administered 28 doses in total of ketotifen/indomethacin combination.

Drug: Ketotifen/Indomethacin

Placebo

PLACEBO COMPARATOR

Placebo pills matching in appearance to study drug twice a day for 28 doses total.

Drug: Placebo

Interventions

Ketotifen/Indomethacin DRUG

2 mg tablet, 75 mg SR tablet

Also known as: Zaditor, Indocin SR, Tivorbex

Study Drug

Placebo DRUG

Matching placebo tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients aged 18-75 years
• Has SARS-CoV-2-positive antigen or molecular diagnostic test (validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay from a sample collected no more than 7 days prior to enrollment.
• At least two signs or symptoms of disease consistent with acute COVID-19 infection. One of these two symptoms must include cough OR shortness of breath with onset within 7 days prior to randomization. Other symptoms that qualify include:
• Fever
• nausea
• vomiting
• diarrhea
• muscle aches
• fatigue
• headache
• loss of smell or taste
• others that are consistent with acute COVID-19 infection in the opinion of the Investigator.
• Able and willing to give written or oral informed consent
• Willing to be an outpatient from Study Day 1 to 14, to provide blood during patient visits on Study Days 1, 3, 5, and 10, return on Study Days 1, 3, 5, 7, 10, 14, and 21 for assessment.
• Willing to keep a diary of pain medication usage, side effects, and COVID-19 associated symptoms and answer a follow-up questionnaire on Study Day 84.

You may not qualify if:

• Clinical signs and symptoms for severe COVID-19, such as:
• Need for hospitalization at the time of screening
• Need for supplemental O2 at the time of screening
• A person with any of the following laboratory values:
• AST or ALT \>/= 1000 U/L
• Known serum creatinine \> 1.6 mg/dL
• Prior use of any of the following treatments: COVID-19 convalescent plasma, monoclonal antibodies against SARS-CoV-2, IVIG (for COVID-19), or COVID-19 treatments (authorized, approved, or investigational)
• Current usage (within the last 7 days prior to randomization) of any of the following drugs:
• anticoagulant drugs including, but not limited to, aspirin, warfarin, or clopidogrel.
• systemic corticosteroids or non-steroidal anti-inflammatory medications for any indication
• drugs that are known to block the functions of ketotifen, such as propranolol.
• oral anti-diabetic agents
• diflunisal or other drugs (or drugs at certain doses) that are contraindicated for concurrent use with Indomethacin
• Prior vaccination of at least one dose of vaccine for SARS-CoV-2
• Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational drug SARS-CoV-2

Sponsors & Collaborators

• Sen-Jam Pharmaceutical: lead
• National University of Singapore: collaborator

Study Sites (2)

Dhulikhel Hospital

Kavre, Bagmati, Nepal

Location

Global Clinical Research Pvt. Ltd.

Kathmandu, 44600, Nepal

Location

Related Publications (5)

• St John AL, Rathore APS. Early Insights into Immune Responses during COVID-19. J Immunol. 2020 Aug 1;205(3):555-564. doi: 10.4049/jimmunol.2000526. Epub 2020 Jun 8.

  PMID: 32513850 BACKGROUND

• Abraham SN, St John AL. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol. 2010 Jun;10(6):440-52. doi: 10.1038/nri2782.

  PMID: 20498670 BACKGROUND

• St John AL, Abraham SN. Innate immunity and its regulation by mast cells. J Immunol. 2013 May 1;190(9):4458-63. doi: 10.4049/jimmunol.1203420.

  PMID: 23606723 BACKGROUND

• Rathore AP, St John AL. Protective and pathogenic roles for mast cells during viral infections. Curr Opin Immunol. 2020 Oct;66:74-81. doi: 10.1016/j.coi.2020.05.003. Epub 2020 Jun 18.

  PMID: 32563779 BACKGROUND

• Kiani P, Scholey A, Dahl TA, McMann L, Iversen JM, Verster JC. In Vitro Assessment of the Antiviral Activity of Ketotifen, Indomethacin and Naproxen, Alone and in Combination, against SARS-CoV-2. Viruses. 2021 Mar 26;13(4):558. doi: 10.3390/v13040558.

  PMID: 33810356 BACKGROUND

MeSH Terms

Interventions

Ketotifen; Indomethacin; ketotifen fumarate ophthalmic solution

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Alexander T Limkakeng, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be provided identical appearing pills
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 16, 2021
• Study Start: May 3, 2022
• Primary Completion: June 20, 2024
• Study Completion: June 20, 2024
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NE (2)