Non-critical patients, hospitalized within the previous 24 hours who tested positive for COVID-19 and have a prior history of cardiovascular disease (CVD) and/or significant risk factors for CVD will be treated for 28 days.
Multi-center, double-blind, randomized, placebo-controlled, parallel group design. 1:1
randomization.
Screening (Day 0-1): Patients hospitalized for COVID-19 within the past 24 hours will be
screened. If patient consent can be obtained, baseline assessments will be carried out:
Physical examination (including vital signs), ECG including QTc interval assessment,
echocardiogram to measure left-ventricular ejection fraction (LVEF), chest X-ray, local
laboratory (including CBC, AST/ALT, alkaline phosphatase, bilirubin, creatinine/eGFR, INR,
pregnancy test (in women with child-bearing potential only), lymphocyte count and LDH. A
C-SSRS will also be completed. Frozen plasma will be retained for central analysis of
CardiolRx™ levels, hs-troponin, NT-proBNP, D-dimer as well as inflammatory markers (hs-CRP,
ferritin, TNF-alpha, IL-1 beta, IL-6, IL-10).
If all eligibility criteria are met, the patient will be randomized to either CardiolRx™ or
placebo.
Study treatment will be initiated immediately after all baseline assessments have been
completed and the patient is randomized (Day1). Oral administration is as follows:
- Day 1 and Day 2: Initial dose: 2.5 mg/kg of body weight b.i.d. with food: CardiolRx™ or
placebo
- Day 3 and Day 4: Increased to 5 mg/kg of body weight b.i.d. with food: CardiolRx™ or
placebo
- Day 5 to Day 28: Increased to 7.5 mg/kg of body weight b.i.d. with food: CardiolRx™ or
placebo For the first 7 days and on Day 10, an ECG will be recorded 4 hours post morning
dose with QTc intervals measured. If the QTc interval is >500 msec or an increase of >
60 msec from baseline is observed, the study medication must be stopped immediately.
If the next higher dose is not tolerated for other reasons, the dose will be reduced to the
previous tolerated dose. The highest tolerated dose will be administered until Day 28.
If the patient is discharged before Day 10, the assessments up to Day 10 will be carried out
as home visits. After Day 10, all remaining scheduled assessments will be carried out during
out-patient visits (or home visits, if out-patient visits are not feasible).
In addition to prolongation of the QTc intervals, careful observation is required to detect
other Adverse Drug Reactions (ADRs) and Drug-Drug Interactions (DDIs). Because CardiolRx™,
may inhibit the metabolism of other drugs, new symptoms may represent toxicity from a
concomitant medication that had previously been well tolerated.
A nasopharyngeal swab will also be done every day until Day 7 and on Day 14 to test for
presence of the SARS-CoV-2 virus.
After Day 7, assessments will be carried out on a weekly basis except for as noted above on
Day 10.
Frozen plasma will be retained for central analysis of CardiolRx™ levels, hs-troponin,
NT-proBNP, D-dimer, inflammatory markers (hs-CRP, ferritin, TNF-alpha, IL-1 beta, IL-6,
IL-10) and additional parameters of interest every two days until Day 7 as well as on day 28.
The assessments on Day 28 include the following: Physical examination (including vital
signs), ECG (recorded 4 hours post morning dose for measurement of QTc interval),
echocardiogram to measure LVEF, chest X-ray, local laboratory assessments, including CBC,
AST/ALT, alkaline phosphatase, bilirubin, creatinine/eGFR, INR, lymphocyte count and LDH. In
addition, a C-SSRS will be completed and the patient will be asked to answer a PICQ.
Further follow-up visits are scheduled for Day 45 and Day 60 post randomization. These
include a clinical assessment (including vital signs) as well as the completion of the PICQ
(PICQ on Day 60 only). Any changes in concomitant medications and (S)AEs will also be
recorded.
Drug: Cannabidiol, pharmaceutically produced with < 5 ppm THC
CardiolRx 2.5 mg/kg to 7.5 mg/kg of body weight b.i.d taken orally with food
Other Name: CardiolRx
Drug: Placebo
Placebo 2.5 mg/kg to 7.5 mg/kg of body weight b.i.d taken orally with food
Inclusion Criteria:
1. Males and females 18 years of age or older 2. Hospitalized for COVID-19 with the most
recent test positive*; not receiving or likely to receive invasive mechanical ventilation
within the next 24 hours 3. Prior history of at least one of: i) CVD [cardiovascular (CV),
cerebrovascular or peripheral vascular diagnoses], ii) Age > 64, iii) Diabetes (DM), iv)
Hypertension (HTN), v) Abnormal serum lipids, vi) Obesity (BMI > or equal 30 or waist
circumference >102 cm [40"] for men and >88 cm [35"] for women), vii) Current smoker
* Must be PCR test.
Exclusion Criteria:
1. Patients who have received vasopressors, extracorporeal membrane oxygenation and
mechanical ventilation within last 30 days
2. Background of cardiac transplant surgery
3. Implanted defibrillator (ICD) in the last three months
4. Implanted left-ventricular assist device (LVAD)
5. Acute coronary syndrome (ACS) within 30 days
6. Percutaneous coronary intervention (PCI) within 30 days
7. Receiving any immuno-suppressive agent other than dexamethasone
8. History of QTc interval prolongation
9. QTc interval > 500 msec
10. Treated with strong inducers of CYP3A4 or CYP2C19
11. Chronic renal failure, determined as eGFR < 30 ml/min
12. Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times
the upper limit of normal (ULN) or ALT or AST >3x ULN plus bilirubin >2x ULN
13. Bacterial sepsis, defined as documented bacteremia at the time of presentation or
other active bacterial infection
14. Current participation in any research study involving investigational drugs or devices
with the exception of dexamethasone, remdesivir, baricitinib plus remdesivir,
convalescent plasma or monoclonal antibodies against the SARS-CoV-2 virus or any other
therapy approved under emergency use in the region for treatment of COVID-19
15. Inability or unwillingness to give informed consent
16. Ongoing drug, alcohol or cannabis abuse
17. Women who are pregnant or breastfeeding
18. Any factor, which would make it unlikely that the patient can comply with the study
procedures
19. Hemoglobin <8.5 gm/dL
20. Leukocyte count < 3000/ mm3
21. Platelets < 100,000 / mm3
22. Current diagnosis of cancer, with the exception of non-melanoma skin cancer
23. Showing suicidal tendency as per the Columbia-Suicide Severity Rating Scale (C-SSRS)
administered at screening
24. Any cannabinoid intake in the past month
25. Body weight > 170 kg
Valleywise Health Medical Center
Phoenix, Arizona, United States
JY Research Institute
Cutler Bay, Florida, United States
Westchester General Hospital
Miami, Florida, United States
University of South Florida
Tampa, Florida, United States
Prairie Education and Research Cooperative
Springfield, Illinois, United States
University of Texas Health Science Center
San Antonio, Texas, United States
Baylor Scott & White Health - Temple
Temple, Texas, United States
Science Valley Research Institute
Campo Largo, Parana, Brazil
Universidade Estadual de Maringa
Maringa, Parana, Brazil
Hospital São Lucas PUCRS
Porto Alegre, Rio Grande Do Sul, Brazil
Irmandade Santa Casa de Misericórdia
Porto Alegre, Rio Grande Do Sul, Brazil
Núcleo de Ensino e Pesquisa do Instituto Mário Penna
Conjunto ACM, Santa Maria, Brazil
Fundação Pio XII - Hospital de Amor Barretos
Barretos, Sao Paulo, Brazil
IPECC-Instituto de Pesquisa Clínica de Campinas
Campinas, Sao Paulo, Brazil
Instituto do Coração do HCFMUSP
Cerqueira César, Sao Paulo, Brazil
SVRI- Irmandade de Santa Casa de Misercordia de Santos
Jabaquara, Sao Paulo, Brazil
Science Valley Research Institute
Santo André, Sao Paulo, Brazil
Fundação Faculdade Regional de Medicine de Sao Jose do Rio Preto (SJRP)
São José Do Rio Preto, Sao Paulo, Brazil
Complexo Hospitalar de Niteroi- Centro de Pesquisa Clinica
Rio de Janeiro, Brazil
TecSalud
Monterrey, Nuevo Leon, Mexico
Dennis McNamara, MD, Study Chair
University of Pittsburgh