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Rationale and design of the cyclosporine in Takotsubo syndrome (CIT) trial
Bastian Bruns1, Nesrin Elsous2, Ina Burghaus3
1Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, Germany; Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany; Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany; German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg/Mannheim, Germany.
Insights
This pilot trial investigates cyclosporine A (CsA) for Takotsubo syndrome (TTS), aiming to reduce myocardial damage. Results may establish CsA as a novel, pathophysiology-driven treatment for TTS.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Takotsubo syndrome (TTS) presents significant morbidity and mortality, with spontaneous ejection fraction recovery.
- Catecholamine excess is implicated in TTS, potentially causing myocardial inflammation and damage.
- No current evidence-based treatment exists for TTS.
Purpose of the Study:
- To investigate the impact of cyclosporine A (CsA) bolus therapy versus placebo in high-risk acute TTS patients.
- To assess CsA's effect on reducing myocardial damage, measured by high-sensitive cardiac Troponin T (hs-cTnT) levels.
- To evaluate CsA's safety and potential as a pathophysiology-driven treatment for TTS.
Main Methods:
- Pilot multicenter, double-blinded, randomized placebo-controlled trial (RCT).
- Patients randomized 1:1 to receive intravenous CsA bolus or placebo.
- Primary endpoint: reduction in AUC of hs-cTnT over 72 hours; secondary endpoints include cardiac function, edema, and clinical outcomes.
Main Results:
- This section is not applicable as the study is ongoing or results are not yet published.
Conclusions:
- The CIT trial will assess CsA's safety and efficacy in reducing myocardial injury marker hs-cTnT in high-risk TTS patients.
- Results could position CsA as the first pathophysiology-driven treatment for TTS, potentially leading to a phase III trial.
Background:
Takotsubo syndrome (TTS) is associated with substantial morbidity and mortality, even though ejection fraction frequently recovers spontaneously. TTS has been suggested to be caused by catecholamine excess leading to myocardial inflammation as an additional driver of cardiac damage and impaired outcome. Currently, no evidence-based treatment exists. In a preclinical model of catecholamine-driven TTS, cyclosporine A (CsA) bolus therapy significantly improved outcome, likely mediated via suppression of calcineurin-driven inflammation. The Cyclosporine In Takotsubo syndrome (CIT) trial is a pilot multicenter double-blinded randomized placebo-controlled trial (RCT) to investigate the impact of CsA bolus therapy in patients suffering from acute TTS.
Study Design And Objectives:
This RCT is designed to investigate the impact of repetitive CsA bolus therapy vs. placebo in acute high-risk TTS patients with an increased risk of intrahospital complications and long-term mortality. The main goal is to reduce myocardial damage quantified by AUC of a centrally measured high-sensitive cardiac Troponin T (hs-cTnT) over 72 hours (primary endpoint). Therefore, patients with TTS will be randomized 1:1 after angiography and receive an intravenous bolus of 2.5 mg/kg CsA or an equivalent amount of placebo immediately after baseline measurements. At 12 and 24 hours additional doses of the study drug will be applied accumulating to 7.5 mg/kg in the intervention group. After baseline laboratory measurements (including hs-cTnT) and echocardiography (TTE), serum parameters will be measured again at 3 hours and every 12 hours from baseline. TTE imaging will be performed at 24, 48 and 72 hours, and cardiac magnetic resonance imaging (CMR) at 24 to 96 hours. Left ventricular function recovery, myocardial edema (CMR), in-hospital complications, length of hospital stay, 30-day and 1-year composite cardiovascular outcome, as well as Kansas City Cardiomyopathy Questionnaire self-assessment are included as secondary endpoints.
Conclusions:
The CIT trial is designed to assess the safety and potential benefit of CsA on hs-cTnT release as an established marker of myocardial injury in high-risk TTS patients. The results of this trial may reveal CsA as a first pathophysiology-driven treatment option of TTS and enable a phase III follow-up trial powered for clinical outcome parameters as primary endpoint.
Clinical Trials Identifier:
NCT05946772.
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