COVID-19
Conditions
Brief summary
This study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.
Interventions
DRUGTelmisartan 40mg
Angiotensin Receptor Blocker (ARB)
DRUGPlacebo
Placebo once daily
Sponsors
National Institute on Minority Health and Health Disparities (NIMHD)
University of Hawaii
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Placebo controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to provide written informed consent prior to initiation of any study procedures. * Understands and agrees to comply with planned study procedures including self testing of blood pressure daily * Male or non-pregnant female adult ≥18 years of age at time of enrolment. * Has laboratory-confirmed severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection as determined by FDA-approved commercial or public health assay in any specimen collected ideally \< 72 hours prior to randomization. Exceptions to the \<72 hr inclusion criteria may be made at the discretion of the investigator. * Positive for COVID-19 symptoms: fever defined as a temperature of \>100.4 on study screening or self-report of daily fever at home OR shortness of breath of any degree OR fatigue causing greater than minimal interference with usual social & functional activities * Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study * Able to easily swallow pills
Exclusion criteria
* Immediate need for hospitalization on screening * Systolic blood pressure less than 100 mmHg * Self-reported presence of chronic kidney disease or requiring dialysis * Self-reported history of liver failure or untreated hepatitis B or C * Pregnancy or breast feeding * Allergy to the study medication * Current use of angiotensin receptor blocker (ARB) or angiotensin converting enzyme (ACE) Inhibitor medications. Other blood pressure medications will be permitted in the systolic BP is higher than 90 mmHg * Prior reaction or intolerance to ARB or ACE Inhibitor * Use of aliskiren in patients with diabetes * Current use of and on-going need for lithium, digoxin, potassium sparing diuretics such as spironolactone * Current use of and need for potassium supplements * Current or past participation in a research study within 12 weeks prior to the Screening Visit unless cleared by Study Team * Inability to drive safely for study visits * Subjects, who, in the opinion of the investigator, are unable to comply with the protocol evaluation, or for whom study participation may not be advisable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Clinical Severity of Disease Since Entry | maximum clinical severity of disease post entry evaluated over the 21 day clinical study | We utilized the World Health Organization (WHO) COVID-19 7-point ordinal scale: 1 (not hospitalized, no limitations on activities), 2 (not hospitalized limitation on activities); 3 (hospitalized, not requiring oxygen); 4 (hospitalized and requiring oxygen); 5 (hospitalized, on non-invasive ventilation or high flow oxygen devices); 6 (hospitalized, on invasive mechanical ventilation or ECMO) and 7 (death). A symptom scale was devised to allow 'fine tuning' within the 2.0 WHO category of 'not hospitalized but limitation on activities' based on severity (no symptoms, mild, moderate, moderately severe and severe symptoms) of fever, breathing and fatigue severity scale (0 to 4 points for each factor allowing a max score of 12). A WHO scale within the '2' category was then 'fine tuned' as follows: 2.0 (\</=3 symptom points), 2.25 (4-6 symptom points), 2.5 (7-9 symptom points), and 2.75 (10-12 symptom points). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Through study completion at day 21 of study | Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014 |
Countries
United States
Participant flow
Recruitment details
Recruitment was advertised generally via physicians and clinics connected with our research center as well as via our medical school's community relations outreach office. Because of the communicable nature of acute COVID-19 infection, the participants were screened, enrolled and underwent their study visits under a portable tent just outside our research clinic on the grounds of the medical school.
Pre-assignment details
No pre-assignment events.
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan Telmisartan 40 mg po daily x 21 days
Telmisartan 40mg: Angiotensin Receptor Blocker (ARB) | 12 |
| Placebo Placebo
Placebo: Placebo once daily | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Telmisartan | Placebo | Total |
|---|---|---|---|
| Age, Continuous mean age | 35.83 years STANDARD_DEVIATION 12.445 | 35.83 years STANDARD_DEVIATION 11.991 | 35.83 years STANDARD_DEVIATION 11.952 |
| Clinical Status | 2.125 units on a scale | 2.00 units on a scale | 2.00 units on a scale |
| Race/Ethnicity, Customized Asian Asian | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than One Race | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Maximum Clinical Severity of Disease Since Entry
We utilized the World Health Organization (WHO) COVID-19 7-point ordinal scale: 1 (not hospitalized, no limitations on activities), 2 (not hospitalized limitation on activities); 3 (hospitalized, not requiring oxygen); 4 (hospitalized and requiring oxygen); 5 (hospitalized, on non-invasive ventilation or high flow oxygen devices); 6 (hospitalized, on invasive mechanical ventilation or ECMO) and 7 (death). A symptom scale was devised to allow 'fine tuning' within the 2.0 WHO category of 'not hospitalized but limitation on activities' based on severity (no symptoms, mild, moderate, moderately severe and severe symptoms) of fever, breathing and fatigue severity scale (0 to 4 points for each factor allowing a max score of 12). A WHO scale within the '2' category was then 'fine tuned' as follows: 2.0 (\</=3 symptom points), 2.25 (4-6 symptom points), 2.5 (7-9 symptom points), and 2.75 (10-12 symptom points).
Time frame: maximum clinical severity of disease post entry evaluated over the 21 day clinical study
Population: Participants with acute COVID infection and symptoms
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Telmisartan | Maximum Clinical Severity of Disease Since Entry | 2.00 score on a scale |
| Placebo | Maximum Clinical Severity of Disease Since Entry | 2.000 score on a scale |
p-value: 0.244Wilcoxon (Mann-Whitney)
Secondary
Number of Adverse Events
Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014
Time frame: Through study completion at day 21 of study
Population: All participants entered into the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telmisartan | Number of Adverse Events | nasal congestion | 1 adverse events |
| Telmisartan | Number of Adverse Events | shortness of breath | 0 adverse events |
| Telmisartan | Number of Adverse Events | chest discomfort | 1 adverse events |
| Telmisartan | Number of Adverse Events | nausea | 1 adverse events |
| Telmisartan | Number of Adverse Events | diarrhea | 1 adverse events |
| Telmisartan | Number of Adverse Events | headache | 1 adverse events |
| Placebo | Number of Adverse Events | diarrhea | 0 adverse events |
| Placebo | Number of Adverse Events | nasal congestion | 1 adverse events |
| Placebo | Number of Adverse Events | nausea | 0 adverse events |
| Placebo | Number of Adverse Events | shortness of breath | 1 adverse events |
| Placebo | Number of Adverse Events | headache | 1 adverse events |
| Placebo | Number of Adverse Events | chest discomfort | 0 adverse events |
p-value: >0.5Kruskal-Wallis