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

February 5, 2024 updated by: Cardiol Therapeutics Inc.

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

Recruiting

Conditions

Intervention / Treatment

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 (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Belo Horizonte, Brazil
        • Recruiting
        • Hospital Felicio Rocho - Fundação Felice Rosso
        • Contact:
          • Maria da Consolação Vieira Moreira, MD
      • Campina Grande Do Sul, Brazil
      • Porto Alegre, Brazil
      • Rio de Janeiro, Brazil
        • Recruiting
        • Hospital Pró-Cardíaco
        • Contact:
          • Marcelo Westerlund Montera, MD
        • Principal Investigator:
          • Marcelo Westerlund Montera
      • Rio de Janeiro, Brazil, 22281-100
        • Recruiting
        • Instituto D´Or de Pesquisa e Ensino
        • Contact:
          • Denilson Campos de Albuquerque
      • São José, Brazil
      • São Paulo, Brazil
      • São Paulo, Brazil, 01223-001
        • Recruiting
        • Irmandade da Santa Casa de Misericordia de Sao Paulo
        • Contact:
          • Ariane Vieira Scarlatelli Macedo
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30210090
        • Recruiting
        • NUPEC-Orizonti
        • Contact:
    • PR
      • Curitiba, PR, Brazil, 80230-130
        • Recruiting
        • PUC trials
        • Contact:
          • LIdia Moura, MD
    • RS
      • Porto Alegre, RS, Brazil, 90035-001
      • Porto Alegre, RS, Brazil, 90035-003
        • Recruiting
        • Hospital de Clinicas de Porto Alegre (HCPA)
        • Contact:
    • Rio De Janeiro
      • Niterói, Rio De Janeiro, Brazil, 24020-096
        • Recruiting
        • Complexo Hospitalar de Niterói
        • Contact:
          • Aurea Grippa, MD
    • SP
      • São Paulo, SP, Brazil, 01409-002
        • Recruiting
        • Hospital Nove de Julho
        • Contact:
          • Thais Pinheiro Lima, MD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G2B7
        • Withdrawn
        • University of Alberta Hospital
    • Quebec
      • Montréal, Quebec, Canada, H4A 3J1
        • Recruiting
        • McGill University Health Centre
        • Contact:
        • Principal Investigator:
          • Matthias Friedrich, Dr.
  • France
      • Bron, France, 69500
        • Recruiting
        • Hopital Louis Pradel Hospices Civils de Lyon
        • Contact:
          • Thomas Bochaton
      • Montpellier, France, 34295
        • Recruiting
        • CHU de Montpellier
        • Contact:
          • François ROUBILLE, MD
      • Nîmes, France, 30029
        • Recruiting
        • Centre Hospitalier Universitaire de Nimes
        • Contact:
          • Benoit LATTUCA
      • Paris, France
        • Recruiting
        • Hôpital Européen Georges-Pompidou
        • Contact:
          • Etienne Puymirat, MD
      • Paris, France
        • Recruiting
        • Institut de Cardiologie hopital Pitié Salpêtrière
        • Contact:
          • Mathieu Kerneis, MD
      • Paris, France
        • Recruiting
        • Hopital Bichat Claude Bernard
        • Contact:
          • Jeremie Abtan, MD
      • Paris, France, 75475
        • Recruiting
        • Hôpital Lariboisière - Département de Cardiologie
        • Contact:
          • Theo PEZEL, MD
      • Poitiers, France
        • Recruiting
        • Centre Hospitalier Universitaire de Poitiers
        • Contact:
          • Claire BOULETI, MD
      • Suresnes, France, 92150
        • Recruiting
        • Hopital Foch
        • Contact:
          • Florent HUANG, MD
      • Toulouse, France
        • Recruiting
        • CHU Rangueil
        • Contact:
          • Clément Delmas, MD
  • Israel
      • Ashkelon, Israel, 7830604
        • Recruiting
        • Barzilai Medical Center
        • Contact:
        • Principal Investigator:
          • Xavier Alejandro Piltz, Dr.
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center
        • Contact:
        • Principal Investigator:
          • Amir Orlev
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Beilinson Hospital, Rabin medical Center
        • Contact:
        • Principal Investigator:
          • Alon Eisen, Prof.
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Tel Aviv Sourasky Medical Center (Ichilov)
        • Contact:
        • Principal Investigator:
          • Yaron Arbel, Prof.
      • Zrifin, Israel, 70300
        • Recruiting
        • Shamir Medical Center (Assaf Harofeh)
        • Contact:
        • Principal Investigator:
          • Gil Moravsky, Dr.
  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Recruiting
        • MedStar Heart and Vascular Institute
        • Contact:
        • Principal Investigator:
          • Mark Hofmeyer, Dr.
    • Florida
      • Miami Lakes, Florida, United States, 33016
        • Withdrawn
        • Palm Springs Community Health Centre
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital site
        • Contact:
        • Principal Investigator:
          • Daniel Zlotoff, Dr.
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Minneapolis Heart Institute Foundation
        • Principal Investigator:
          • David Lin, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Pavan Bhat, Dr.
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University
        • Contact:
        • Principal Investigator:
          • Roshanak Markley, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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)
Time Frame: 12 weeks post randomization
primary
12 weeks post randomization
Global longitudinal Strain (GLS)
Time Frame: 12 weeks post randomization
primary
12 weeks post randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left-ventricular ejection fraction (LVEF)
Time Frame: 12 weeks post randomization
secondary endpoint
12 weeks post randomization

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients recovered
Time Frame: From baseline to 12 weeks of treatment
defined as LVEF ≥ 0.55 at 12 weeks of treatment
From baseline to 12 weeks of treatment
Survival, free from major event
Time Frame: 12 weeks post randomization
Major event defined as cardiac transplant, left-ventricular assist device (LVAD), hospitalization for Heart failure (HF)
12 weeks post randomization
Change in CMR parameters (%)
Time Frame: From baseline to 12 weeks of treatment

Any change in CMR parameters from baseline to 12 weeks post randomization:

LVEF (%), ECV (%), GLS (%), LGE (%)
From baseline to 12 weeks of treatment
Change in CMR parameters (mL/m2)
Time Frame: From baseline to 12 weeks of treatment

Any change in CMR parameters from baseline to 12 weeks post randomization:

LVEDV (ml/m2), LVESV (ml/m2), LAESV (ml/m2).
From baseline to 12 weeks of treatment
Change in CMR parameters (g/m2)
Time Frame: From baseline to 12 weeks of treatment

Any change in CMR parameters from baseline to 12 weeks post randomization:

LV mass (g/m2)
From baseline to 12 weeks of treatment
New York Heart Association classification (NYHA)
Time Frame: From baseline to 12 weeks of treatment

New York Heart Association classification (NYHA) ranked in order of best to worse outcome from Class I (best) to Class IV (worst).

Record any change from baseline in percentage of patients in NYHA class IV/III/II class over the course of 12 weeks.
From baseline to 12 weeks of treatment
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: From baseline to 12 weeks of treatment
Any changes from baseline KCCQ compared to after 12 weeks of treatment Where "No limits" is the best outcome and "Severely limited" is the worst outcome.
From baseline to 12 weeks of treatment
Time to resolution of clinical symptoms
Time Frame: From baseline to 12 weeks of treatment
chest pain, arrhythmias, shortness of breath
From baseline to 12 weeks of treatment
Changes in inflammatory and biomarker hs-troponin (nh/ml)
Time Frame: From baseline to 12 weeks of treatment

Patients with myocarditis present with abnormal (very high) values in inflammatory and biomarkers.

The investigators are trying to determine if CardiolRx normalizes them faster than placebo.
From baseline to 12 weeks of treatment
Changes in inflammatory and biomarkers NT-proBNP (pg/ml), TNF-alpha (pg/ml), IL-1 beta (pg/ml) and IL-6 (pg/ml)
Time Frame: From baseline to 12 weeks of treatment

Patients with myocarditis present with abnormal (very high) values in inflammatory and biomarkers.

The investigators are trying to determine if CardiolRx normalizes them faster than placebo.
From baseline to 12 weeks of treatment
Changes in inflammatory and biomarkers hs-CRP (mg/l), and ferritin (mg/l)
Time Frame: From baseline to 12 weeks of treatment

Patients with myocarditis present with abnormal (very high) values in inflammatory and biomarkers.

The investigators are trying to determine if CardiolRx normalizes them faster than placebo.
From baseline to 12 weeks of treatment
Changes in inflammatory and biomarker IL-10 (ng/ml)
Time Frame: From baseline to 12 weeks of treatment

Patients with myocarditis present with abnormal (very high) values in inflammatory and biomarkers.

The investigators are trying to determine if CardiolRx normalizes them faster than placebo.
From baseline to 12 weeks of treatment
Normalization of prognostically important ECG changes
Time Frame: From baseline to 12 weeks of treatment
Time to normalization of normalization of PR interval
From baseline to 12 weeks of treatment
Normalization of prognostically important ECG changes
Time Frame: From baseline to 12 weeks of treatment
Time to normalization of normalization of QRS duration
From baseline to 12 weeks of treatment
Normalization of prognostically important ECG changes
Time Frame: From baseline to 12 weeks of treatment
Time to normalization of normalization of ST/T wave changes
From baseline to 12 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardiol Therapeutics Inc.

Investigators

  • Study Chair: Dennis McNamara, MD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 22, 2022

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 1, 2024

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)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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