Clinical trial NCT04435015: The Utility of Camostat Mesylate in Patients With COVID-19 Associated Coagulopathy (CAC) and Cardiovascular Complications
Official title: The Utility of Camostat Mesylate in Patients With COVID-19 Associated Coagulopathy (CAC) and Cardiovascular Complications
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Coagulopathy
Cardiovascular Complication
COVID-19
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2020-06-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aim of this study is to determine whether Camostat mesylate reduces SARS-COV-2 associated coagulopathy. Additional aims are to determine the effect of Camostat mesylate on SARS-COV-2 associated myocardial injury, to assess duration of hypoxia or intubation, to evaluate the length of intensive care unit and hospital stay, and assess mortality rates.

Detailed description: The trial is in-patient only. Participants are identified by the hospital physicians and house staff, and contacted by research study personnel. Potential participants fulfilling inclusion criteria and not fulfilling exclusion criteria who agree to participate and sign the informed consent undergo the enrollment process. Ono Pharmaceutical, Japan, will provide Camostat mesylate tablets. The Yale New Haven Hospital research pharmacy will receive and store the drug within 15-25C range according to protocol storage requirements.

Microcrystalline Cellulose NF (PH-102) for placebo formulation will be acquired from Fagron. Empty gelatin capsules Size 0, for over-encapsulation will be acquired from Fagron. Before Ono Pharmaceutical can send the drug, an IND will be obtained from the FDA.

Principal Investigator and the Yale New Haven Hospital research pharmacy will keep accountability records for all investigational products acquired, dispensed, used and disposed. Drugs are administered by nurses. There will be no restriction on taking other medications, activities or food intake. There are two arms to the study: (a) pharmacy-formulated placebo 3 times a day (b) 200 mg Camostat mesylate to be taken three times daily. Each arm will have 100 subjects. All patients will receive treatment until discharged. Participants will be randomized equally to Camostat mesylate or identical appearing placebo using a permuted-block design with variable block size. The actual treatment assignment will be concealed from the investigators and the participants. The randomization scheme will be generated by the statistical group.

Participants have the option of refusing study drug. If the participant decides to stop the drug or blood drawing he or she would be dropped from the trial.

Eligibility criteria: Inclusion Criteria:

1. . Positive COVID-19 test result.
2. Diagnosis of COVID-19 associated coagulopathy and cardiac complications based on D-Dimer, fibrinogen, TnT, CTPE, ischemic EKG changes
3. Provision of informed consent. In patients with altered mental status consents can be obtained from the power of attorney.
4. Stated willingness to comply with all study procedures and availability for the duration of the study
5. Male or female, age 18 or older
6. Diagnosed with hypoxia requiring intubation or positive air pressure.
7. Diagnose with DVT/PE by ultrasound and CTPE and/or
8. Elevated D-Dimer and/or
9. Greater than 2-fold increase in TnT
10. Ischemic EKG changes with ST depression or elevation more than 1 mm in 2 consecutive leads
11. Ability to administer oral medication.

Exclusion Criteria:

1. GFR\<30 mL/min
2. Severe bleeding requiring blood transfusion of drop of 5% in HCT.
3. Pregnancy or lactation
4. Known allergic reactions to components of Camostat mesylate.
5. Subjects under age 18

Primary outcomes:
measure: Percent change in plasma D-Dimer
timeFrame: 7 days
Secondary outcomes:
measure: Overall Safety and adverse event
timeFrame: 3 months
measure: Change in plasma Fibrinogen levels
timeFrame: 7 days
measure: Change in plasma troponin
timeFrame: 7 days
measure: New onset cardiomyopathy
timeFrame: 7 days
measure: Duration of intubation
timeFrame: 7 days
measure: Length of stay in the intensive care unit
timeFrame: 28 days
measure: Time to discharge from hospital
timeFrame: 30 days
measure: Occurrence of major adverse cardiovascular events
timeFrame: 7 days
Other outcomes:
Locations:
Study officials:
affiliation: Yale University
name: Arya Mani, MD
role: PRINCIPAL_INVESTIGATOR
References: