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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05946772
Other study ID # DZHK29
Secondary ID DZHK29
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date October 2024
Est. completion date October 2027

Study information

Verified date May 2024
Source University Hospital Heidelberg
Contact Bastian Bruns, MD
Phone +496221-56-36266
Email bastian.bruns@med.uni-heidelberg.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The goal of this clinical trial is to investigate the impact of repetitive acute Cyclosporine A (CsA) bolus therapy in patients suffering from TTS with an elevated risk of impaired outcome. The main question it aims to answer is whether CsA reduces myocardial injury (primary outcome). Participants will receive CsA or placebo at baseline and every 12h in the first 24h after study inclusion. Researchers will compare CsA and the placebo group to see if a) myocardial injury is reduced, and b) ejection fraction is improved compared to baseline, as well as several other secondary endpoints over a one year follow-up.


Description:

Takotsubo syndrome (TTS) has been suggested to be caused by catecholamine excess with myocardial inflammation-enhanced cardiac injury. Substantial morbidity and mortality have repeatedly been reported, even though reduced ejection fraction frequently recovers spontaneously. So far there is no evidence-based treatment available. In a clinically relevant mouse model of catecholamine-driven TTS, cyclosporine A (CsA) bolus therapy markedly improves outcome, likely mediated via suppression of calcineurin-driven inflammation. The investigators have thus designed a pilot multicentre randomized controlled trial (RCT) to investigate the impact of repetitive CsA bolus therapy vs. placebo in acute TTS patients with an increased risk of intrahospital complications and a 32% estimated 5-year mortality. As primary outcome myocardial damage will be compared between groups via high-sensitive Troponin T plasma area under the curve (AUC). Recovery of cardiac function, the extent of myocardial oedema at 72h, length of hospital-stay, 30-day-, and 1-year composite clinical outcome as well as psychosocial and quality of life self-assessment will be secondary endpoints. 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 with outcome parameters as primary endpoint.


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Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Cyclosporine A
2.5mg/kg body weight Cyclosporine A as an intravenous bolus
Placebo
The same amount of 0.9% sodium chloride (NaCl0.9%) will be applied in an indistinguishable package as an intravenous bolus

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Sponsors (3)

Lead Sponsor Collaborator
University Hospital Heidelberg Coordinating Centre for Clinical Studies (KKS) Heidelberg, German Centre of Cardiovascular Research (DZHK)

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Myocardial damage High-sensitive Troponin T AUC over several time points between CsA and Placebo. baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Change in Ejection fraction from baseline Multiple timepoints will be compared to baseline between CsA and Placebo. baseline, hour 24, hour 48, hour 72, day 30
Secondary Fold-change in Troponin plasma concentration The change of high-sensitive Troponin T will be compared to baseline between CsA and Placebo for multiple time points. baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Fold-change in creatine kinase plasma concentration The change of creatine kinase will be compared to baseline between CsA and Placebo for multiple time points. baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Fold-change in NTproBNP plasma concentration The change of NTproBNP will be compared to baseline between CsA and Placebo for multiple time points. baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Fold-change in interleukin-6 plasma concentration The change of interleukin-6 will be compared to baseline between CsA and Placebo for multiple time points. baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Fold-change in procalcitonin plasma concentration The change of procalcitonin will be compared to baseline between CsA and Placebo for multiple time points. baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
Secondary Myocardial edema Cardiac MRI will be used to assess the T2 signal intensity ratio for comparison between CsA and Placebo at 72h. hour 72
Secondary Myocardial inflammation Cardiac MRI will be used to assess the early gadolinium enhancement ratio for comparison between CsA and Placebo at 72h. hour 72
Secondary Rate of cardiovascular events at day 30 At day 30 a composite cardiovascular outcome measure includes overall mortality, stroke, myocardial infarction, heart failure hospitalization, recurrent TTS, cardiac arrest, ventricular fibrillation, ventricular tachycardia, novel atrial fibrillation, and thromboembolism. The measure is considered positive if one of the above occurs. The amount of patients with positive and negative events is then compared between the CsA and placebo arm. day 30
Secondary Rate of cardiovascular events at 1 year At 1 year a composite cardiovascular outcome measure includes overall mortality, stroke, myocardial infarction, heart failure hospitalization, recurrent TTS, cardiac arrest, ventricular fibrillation, ventricular tachycardia, novel atrial fibrillation, and thromboembolism. The measure is considered positive if one of the above occurs. The amount of patients with positive and negative events is then compared between the CsA and placebo arm. 1 year
Secondary Rate of novel disease onset At 30 days and 1-year novel clinical diagnoses during follow-up including cancer or neurological diseases will be assessed. day 30 and at 1 year
Secondary Symptom burden at day 30 Patient-reported outcome will be quantified by the Kansas City Cardiomyopathy Questionnaire after 30d and 1 year (scale 0-100 points: 0-24 points: very poor; 25-49 points: poor; 50-74 points: fair; 75-100: good). day 30
Secondary Symptom burden at 1 year Patient-reported outcome will be quantified by the Kansas City Cardiomyopathy Questionnaire at 1 year (scale 0-100 points: 0-24 points: very poor; 25-49 points: poor; 50-74 points: fair; 75-100: good). 1 year
Secondary Depression score at day 30 Patient-reported psychosocial assessment will be quantified by the well validated German patient health questionnaire 9 (PHQ-9) scale (range 0-27 points, higher points indicate worse depressive symptoms). day 30
Secondary Depression score at year 1 Patient-reported psychosocial assessment will be quantified by the well validated German patient health questionnaire 9 (PHQ-9) scale (range 0-27 points, higher points indicate worse depressive symptoms). 1 year
Secondary Anxiety score at day 30 Patient-reported psychosocial assessment will be quantified by the well validated German generalized anxiety disorder 7 (GAD-7) questionnaire (range 0-21 points, higher points indicate worse anxiety). day 30
Secondary Anxiety score at year 1 Patient-reported psychosocial assessment will be quantified by the well validated German generalized anxiety disorder 7 (GAD-7) questionnaire (range 0-21 points, higher points indicate worse anxiety). year 1
Secondary PTSD score at 30 days Patient-reported psychosocial assessment will be quantified by the well validated German primary care posttraumatic stress disorder questionnaire 5 (PC-PTSD-5) (0-5 points, higher points indicate more symptoms of posttraumatic stress disorder). day 30
Secondary PTSD score at 1 year Patient-reported psychosocial assessment will be quantified by the well validated German primary care posttraumatic stress disorder questionnaire 5 (PC-PTSD-5) (0-5 points, higher points indicate more symptoms of posttraumatic stress disorder). year 1
Secondary Length of intermediate care or intensive care unit stay Length of intermediate care or intensive care unit stay will be compared between groups day 30
Secondary Length of hospital stay Length of hospital stay will be compared between groups day 30
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