TY - JOUR
T1 - Impact of cannabidiol on myocardial recovery in patients with acute myocarditis
T2 - Rationale & design of the ARCHER trial
AU - ARCHER Study Group
AU - McNamara, Dennis M.
AU - Cooper, Leslie T.
AU - Arbel, Yaron
AU - Bhimaraj, Arvind
AU - Bocchi, Edimar
AU - Friedrich, Matthias G.
AU - Kerneis, Matthieu
AU - Liu, Peter
AU - Parker, Andrea B.
AU - Smith, Eldon R.
AU - Tang, W. H.Wilson
AU - Torre-Amione, Guillermo
AU - Tschöpe, Carsten
N1 - Publisher Copyright:
© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
PY - 2024/10
Y1 - 2024/10
N2 - Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results: We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions: The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
AB - Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results: We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions: The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
KW - Anti-inflammatory
KW - CMR
KW - Cannabidiol
KW - Myocarditis
KW - Randomized trial
UR - http://www.scopus.com/inward/record.url?scp=85197459011&partnerID=8YFLogxK
U2 - 10.1002/ehf2.14889
DO - 10.1002/ehf2.14889
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C2 - 38937900
AN - SCOPUS:85197459011
SN - 2055-5822
VL - 11
SP - 3416
EP - 3424
JO - ESC heart failure
JF - ESC heart failure
IS - 5
ER -