Impact of CardiolRx on Myocardial Recovery in Patients With Acute Myocarditis (ARCHER)
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ClinicalTrials.gov Identifier: NCT05180240 |
Recruitment Status :
Recruiting
First Posted : January 6, 2022
Last Update Posted : February 7, 2024
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Tracking Information | |||||||||
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First Submitted Date ICMJE | September 25, 2021 | ||||||||
First Posted Date ICMJE | January 6, 2022 | ||||||||
Last Update Posted Date | February 7, 2024 | ||||||||
Actual Study Start Date ICMJE | June 22, 2022 | ||||||||
Estimated Primary Completion Date | November 2024 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
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Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
Left-ventricular ejection fraction (LVEF) [ Time Frame: 12 weeks post randomization ] secondary endpoint
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Impact of CardiolRx on Myocardial Recovery in Patients With Acute Myocarditis | ||||||||
Official Title ICMJE | Impact of CardiolRx on Myocardial Recovery in Acute Myocarditis. A Double-blind, Placebo-controlled Trial | ||||||||
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. |
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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
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. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Multi-center, double-blind, randomized, placebo-controlled, parallel group design. 1:1 randomization Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Placebo will match active study drug in color, odor, taste and appearance to assure proper blinding. Primary Purpose: Treatment
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Condition ICMJE | Acute Myocarditis | ||||||||
Intervention ICMJE | Drug: CardiolRx
Eligible patients will be randomized to receive CardiolRx or placebo. Intervention will be administered orally (via syringe) with food twice daily.
Other Name: Cannabidiol
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Study Arms ICMJE |
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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. | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
100 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2024 | ||||||||
Estimated Primary Completion Date | November 2024 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Brazil, Canada, France, Israel, United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT05180240 | ||||||||
Other Study ID Numbers ICMJE | Cardiol 100-002 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Cardiol Therapeutics Inc. | ||||||||
Original Responsible Party | Same as current | ||||||||
Current Study Sponsor ICMJE | Cardiol Therapeutics Inc. | ||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | Cardiol Therapeutics Inc. | ||||||||
Verification Date | February 2024 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |