Impact of CardiolRx on Myocardial Recovery in Patients With Acute Myocarditis (ARCHER)

Impact of CardiolRx on Myocardial Recovery in Acute Myocarditis. A Double-blind, Placebo-controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Acute Myocarditis
• Intervention / Treatment: Drug: CardiolRx

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.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • Hospital Felicio Rocho - Fundação Felice Rosso
  • Campina Grande do Sul, Brazil
    • Hospital Angelina Caron
  • Porto Alegre, Brazil
    • Hospital São Lucas
  • Rio de Janeiro, Brazil, 22281-100
    • Instituto D´Or de Pesquisa e Ensino
  • Rio de Janeiro, Brazil
    • Hospital Pró-Cardíaco
  • São José, Brazil
    • Hospital Regional de São José
  • São Paulo, Brazil
    • Instituto do Coração - InCor
  • São Paulo, Brazil, 01223-001
    • Irmandade da Santa Casa de Misericórdia de São Paulo
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30210090
      • Nupec-Orizonti
  • Paraná
    • Curitiba, Paraná, Brazil, 80230-130
      • PUC trials
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-001
      • Hospital Moinhos de Vento
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
      • Hospital de Clínicas de Porto Alegre (HCPA)
  • Rio de Janeiro
    • Niterói, Rio de Janeiro, Brazil, 24020-096
      • Complexo Hospitalar de Niteroi
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01409-002
      • Hospital Nove de Julho
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2B7
      • University of Alberta Hospital
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• France
  • Bron, France, 69500
    • Hopital Louis Pradel Hospices Civils de Lyon
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nîmes, France, 30029
    • Centre Hospitalier Universitaire de Nīmes
  • Paris, France
    • Hôpital européen Georges-Pompidou
  • Paris, France
    • Hopital Bichat Claude Bernard
  • Paris, France, 75475
    • Hôpital Lariboisière - Département de Cardiologie
  • Paris, France
    • Institut de Cardiologie hopital Pitié Salpêtrière
  • Poitiers, France
    • Centre Hospitalier Universitaire de Poitiers
  • Suresnes, France, 92150
    • Hôpital Foch
  • Toulouse, France
    • CHU Rangueil
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
  • Petah Tikva, Israel, 4941492
    • Beilinson Hospital, Rabin medical Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center (Ichilov)
  • Zrifin, Israel, 70300
    • Shamir Medical Center (Assaf Harofeh)
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Heart and Vascular Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: CardiolRx; Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.; Other Names: Cannabidiol
Placebo Comparator: 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	Drug: CardiolRx; Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.; Other Names: Cannabidiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular Volume (ECV)	Change of ECV from baseline at 12 weeks, measured by cardiac Cardiac MRI. ECV is measuring the degree of edema and fibrosis. The unit of measure was percentage. It was the percentage of myocardial tissue that is extracellular space (i.e. fraction of the myocardium occupied by extracellular matrix and interstitial fluid).	12 weeks post randomization
Global Longitudinal Strain (GLS)	The outcome was the change in GLS from baseline at 12 weeks, measured by cardiac Cardiac MRI. GLS is a predictor of cardiac function. The unit of measure is percentage. It is the percent change in myocardial length relative to its original (end-diastolic) length along the long axis. Longitudinal strain during systole is usually negative, because the ventricle shortens; normal peak GLS in healthy adults is around -20% (i.e., 20% shortening relative to original length)	12 weeks post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left-ventricular Ejection Fraction (LVEF) From Baseline at 12 Weeks	Left-ventricular ejection fraction (LVEF) as measured by Cardiac MRI at 12 weeks. LVEF is a measure of cardiac function. The unit of measure is percentage. It is the percent of end-diastolic blood volume in the left ventricle that is ejected with each systolic contraction. Mathematically, LVEF = (stroke volume/end-diastolic volume) x 100.	12 weeks post randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left-ventricular Mass From Baseline at 12 Weeks	Left-ventricular mass at week 12, measured with cardiac MRI. Unit of measure is grams (g) of myocardium. The mass of left-ventricular myocardial tissue was calculated from lCMR using geometric assumptions (e.g., Devereux/ASE cube formula) and myocardial density.	From baseline to 12 weeks of treatment

Collaborators and Investigators

• Sponsor: Cardiol Therapeutics Inc.
• Investigators: Study Chair: Dennis McNamara, MD, University of Pittsburgh

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2022
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): February 4, 2025

Study Registration Dates

• First Submitted: September 25, 2021
• First Submitted That Met QC Criteria: December 31, 2021
• First Posted (Actual): January 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pharmaceutically produced CBC; THC < 5ppm
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Myocarditis; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: Cardiol 100-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No