Impact of CardiolRx on Myocardial Recovery in Patients With Acute Myocarditis

NCT ID: NCT05180240

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-22
• Study Completion Date: 2025-02-04

Brief Summary

Multi-center, double-blind, placebo-controlled, parallel group design. Patients with myocarditis will be screened and, if eligible, randomized within 10 days of the diagnostic CMR to CardiolRx or placebo.

CardiolRx is pharmaceutically produced Cannabidiol and is free of tetrahydrocannabinol (THC<5 ppm). The treatment period is 12 weeks; a last follow-up visit is scheduled one week after the last treatment, 13 weeks after randomization. Study assessments include Cardiac Magnetic Resonance imaging (CMR), ECG monitoring, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as physical exams and laboratory tests.

The primary and secondary outcome parameters are measured by CMR. Additional outcomes include clinical endpoints and changes in inflammatory and biomarkers.

Detailed Description

Rationale:

Myocarditis is an acute inflammatory condition of the myocardium. Presentation of the disease may be fulminant and necessitate cardiac support, or even result in sudden cardiac death; milder cases are usually self-limiting but may progress to dilated cardiomyopathy with eventual end-stage heart failure. Other than treatments for associated heart failure there are no specific indicated treatments for myocarditis. CardiolRxTM (cannabidiol [CBD] solution), which is known to have anti-inflammatory properties, is being investigated to treat the underlying inflammatory process and thereby favorably modify acute myocarditis. The primary endpoints of the trial are cardiac magnetic resonance measures of left ventricular systolic function (ejection fraction and longitudinal strain) and myocardial edema (extra cellular volume) which have been shown to predict long term prognosis of patients with acute myocarditis.

Multi-center, double-blind, randomized, placebo-controlled, parallel group design. 1:1 randomization; treatment will be stratified within sites.

Patients diagnosed with acute myocarditis by a biopsy or a CMR will be screened within 10 days of the diagnostic CMR. Informed consent will be obtained at this point. For patients who have been diagnosed using an EMB, a CMR needs to be performed as well, which will be included in the informed consent form (ICF).Eligible patients will then be randomized within 10 days from the CMR assessment.

Baseline assessments include the following: Clinical assessment, including vital signs, ECG, 24-hr Holter, chest x-ray; Hematology and blood chemistry, NYHA classification, C SSRS and KCCQ. Frozen plasma will be retained for central analysis of hs-troponin, NT-proBNP and inflammatory markers.

Study treatment needs to be taken with food and will be initiated in the evening of Day 1, after all baseline assessments have been completed and the patient has been randomized.

Oral administration is as follows:

• Week 1 (p.m. dose of Day 1 to a.m. dose of Day 7): 2.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo

• Week 2 (p.m. dose of Day 7 to a.m. dose of Day 14):

5 mg/kg of body weight b.i.d. CardiolRxTM or placebo

• Week 3 (p.m. dose of Day 14 to a.m. dose of Day 21):

7.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo • Week 4 to end of treatment period (p.m. dose of Day 21 to

a.m. dose of last day of treatment period at week 12): 10 mg/kg of body weight b.i.d. CardiolRxTM or placebo

If the next higher dose after each study drug increase is not tolerated, the dose will be reduced to the previous tolerated dose.

Every week (before the next dose increase) the patient will be re-evaluated. This includes ECG monitoring at approximately 5 hours post-morning dose (time of Tmax) to surveil for deleterious effects on ECG intervals (particularly the QTc interval) and rhythm. Drug titration will be dependent on investigator or designate interrogation of the ECGs and the absence of new, clinically significant abnormalities on those ECGs.

Vital signs, concurrent medication and Adverse Events (AEs), including Serious Adverse Events (SAEs) will be recorded, blood chemistry including liver function tests, hematology as well as INR assessments will be carried out.

Final efficacy assessments (including a second CMR) will take place after 12 weeks of study treatment. A final safety assessment will take place after 13 weeks, 1 week after completion of study treatment.

Conditions

Acute Myocarditis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CardiolRx

• Week 1 (p.m. dose of Day 1 to a.m. dose of Day 7): 2.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 2 (p.m. dose of Day 7 to a.m. dose of Day 14): 5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 3 (p.m. dose of Day 14 to a.m. dose of Day 21): 7.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 4 to end of treatment period (p.m. dose of Day 21 to a.m. dose of last day of treatment period at week 12): 10 mg/kg of body weight b.i.d. CardiolRxTM or placebo

Group Type: EXPERIMENTAL

CardiolRx

Intervention Type: DRUG

Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.

Placebo

• Week 1 (p.m. dose of Day 1 to a.m. dose of Day 7): 2.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 2 (p.m. dose of Day 7 to a.m. dose of Day 14): 5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 3 (p.m. dose of Day 14 to a.m. dose of Day 21): 7.5 mg/kg of body weight b.i.d. CardiolRxTM or placebo
• Week 4 to end of treatment period (p.m. dose of Day 21 to a.m. dose of last day of treatment period at week 12): 10 mg/kg of body weight b.i.d. CardiolRxTM or placebo

Group Type: PLACEBO_COMPARATOR

CardiolRx

Intervention Type: DRUG

Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.

Interventions

CardiolRx

Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.

Intervention Type: DRUG

Other Intervention Names

Cannabidiol

Eligibility Criteria

Inclusion Criteria

1. Males and females 18 years of age or older

2. Diagnosed with acute myocarditis including:

1. Clinical criteria (symptoms of chest pain, arrhythmia or shortness of breath, or history of viral-like illness), preferably followed by elevated troponin PLUS

2. CMR diagnosis (Lake Louise Criteria) within 10 days prior to randomization OR

3. Endomyocardial biopsy (EMB) showing either cellular inflammation and/or immunohistochemistry consistent with inflammation.

3. Male subjects with partners of childbearing potential who have had a vasectomy or are willing to use double barrier contraception methods during the conduct of the study and for 2 months after the last dose of study drug.

4. Women of childbearing potential willing to use an acceptable method of contraception starting with study drug administration and for a minimum of 2 months after study completion. Otherwise, women must be post- menopausal.

Exclusion Criteria

1. Coronary artery disease (CAD) defined as a stenosis greater than 50% in a major epicardial coronary artery

2. Severe valvular heart disease

3. Inability to safely undergo CMR including administration of gadolinium

4. Estimated glomerular filtration rate (eGFR) < 30 ml/min

5. 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.

6. Sepsis, defined as documented bacteremia at the time of presentation or other documented active infection.

7. Severe left ventricular (LV) dysfunction requiring inotropic support, left ventricular assist device (LVAD) or other circulatory assist devices, or urgent need for transplantation

8. Documented biopsy evidence of giant cell or eosinophilic myocarditis

9. Prior history of sustained ventricular arrhythmia

10. Acute coronary syndrome within 30 days

11. Percutaneous coronary intervention within 30 days

12. History of QT interval prolongation or QTc interval > 500 msec

13. Treated with strong inducers CYP3A4 or CYP2C19, as listed in Appendix 17.8

14. Treated with digoxin and/or type 1 or 3 antiarrhythmics

15. Current participation in any research study involving investigational drugs or devices

16. Inability or unwillingness to give informed consent

17. Ongoing drug or alcohol abuse

18. Women who are pregnant or breastfeeding

19. Current diagnosis of cancer, with the exception of non-melanoma skin cancer

20. Any factor, which would make it unlikely that the patient can comply with the study procedures

21. On any cannabinoid during the past month

22. Body weight > 170 kg

23. Showing suicidal tendency as per the C-SSRS, administered at screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardiol Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dennis McNamara, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

MedStar Heart and Vascular Institute

Washington D.C., District of Columbia, United States

Massachusetts General Hospital site

Boston, Massachusetts, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Nupec-Orizonti

Belo Horizonte, Minas Gerais, Brazil

PUC trials

Curitiba, Paraná, Brazil

Complexo Hospitalar de Niterói

Niterói, Rio de Janeiro, Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

Hospital de Clínicas de Porto Alegre (HCPA)

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Nove de Julho

São Paulo, São Paulo, Brazil

Hospital Felicio Rocho - Fundação Felice Rosso

Belo Horizonte, , Brazil

Hospital Angelina Caron

Campina Grande do Sul, , Brazil

Hospital São Lucas

Porto Alegre, , Brazil

Instituto D´Or de Pesquisa e Ensino

Rio de Janeiro, , Brazil

Hospital Pró-Cardíaco

Rio de Janeiro, , Brazil

Hospital Regional de São José

São José, , Brazil

Irmandade da Santa Casa de Misericórdia de São Paulo

São Paulo, , Brazil

Instituto do Coração - InCor

São Paulo, , Brazil

University of Alberta Hospital

Edmonton, Alberta, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Hopital Louis Pradel Hospices Civils de Lyon

Bron, , France

CHU de Montpellier

Montpellier, , France

Centre Hospitalier Universitaire de Nîmes

Nîmes, , France

Hôpital Lariboisière - Département de Cardiologie

Paris, , France

Hopital Bichat Claude Bernard

Paris, , France

Hôpital européen Georges-Pompidou

Paris, , France

Institut de Cardiologie hopital Pitié Salpêtrière

Paris, , France

Centre Hospitalier Universitaire de Poitiers

Poitiers, , France

Hôpital Foch

Suresnes, , France

Chu Rangueil

Toulouse, , France

Barzilai Medical Center

Ashkelon, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Beilinson Hospital, Rabin medical Center

Petah Tikva, , Israel

Tel Aviv Sourasky Medical Center (Ichilov)

Tel Aviv, , Israel

Shamir Medical Center (Assaf Harofeh)

Zrifin, , Israel

Countries

United States; Brazil; Canada; France; Israel

References

Lee WS, Erdelyi K, Matyas C, Mukhopadhyay P, Varga ZV, Liaudet L, Hasku G, Cihakova D, Mechoulam R, Pacher P. Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation. Mol Med. 2016 Sep;22:136-146. doi: 10.2119/molmed.2016.00007. Epub 2016 Jan 8.

Reference Type: BACKGROUND

PMID: 26772776 (View on PubMed)

Other Identifiers

Cardiol 100-002

Identifier Type: -

Identifier Source: org_study_id