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NCT Number: NCT05946772

Cyclosporine In Takotsubo Syndrome

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.

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Key information

Conditions

Takotsubo Cardiomyopathy Cardiomyopathies Cardiovascular Diseases Heart Diseases Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Ventricular Dysfunction Ventricular Dysfunction, Left

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Kerckhoff Heart Center, Bad Nauheim / Gießen University, Bad Nauheim, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key inclusion criteria:

  • Patients aged over 18
  • Enrollment and first IMP administration within 24 hours after cardiac catheterization
  • Regional Wall Motion Abnormality (WMA) consistent with TTS in angiography or echocardiography
  • InterTAK prognostic score- or a GEIST Score ≥ 9 -
  • Written informed consent

Key exclusion Criteria:

  • Acute coronary syndrome (ACS) with significant coronary stenosis potentially associated with wall motion abnormalities (WMA) or percutaneous coronary intervention (PCI)
  • Infection (defined as concomitant infection with a positive blood culture at the time of study inclusion)
  • History of hypersensitivity to cyclosporine
  • History of hypersensitivity to egg, peanut or soybean proteins
  • History of chronic renal insufficiency (either creatinin clearance <30 ml/min/1.73m² or current medical care for severe renal insufficiency)
  • History of liver insufficiency
  • Uncontrolled hypertension at the time of screening for study inclusion (systolic blood pressure >180mmHg and/or diastolic blood pressure >110mmHg)
  • Current medication with any compound containing Hypericum perforatum (St. John's worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine (Rosuvastatine >5mg within 24h intake<48h before IMP administration)
  • Female patients currently pregnant or women of childbearing age without negative pregnancy test or without effective contraception
  • Any disorder associated with immunological dysfunction ≤6 months prior to presentation (autoimmune disease, known positive serology for HIV or hepatitis)
  • Immunosuppressive, chemotherapeutical, or antibody treatment
  • Participation in other clinical trials except for non interventional trials

Treatment and study plan

Cyclosporine A

Drug

2.5mg/kg body weight Cyclosporine A as an intravenous bolus

Placebo

Drug

The same amount of 0.9% sodium chloride (NaCl0.9%) will be applied in an indistinguishable package as an intravenous bolus

Primary outcomes

  1. Myocardial damage

    Time frame: baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    High-sensitive Troponin T AUC over several time points between CsA and Placebo.

Secondary outcomes

  1. Change in Ejection fraction from baseline

    Time frame: baseline, hour 24, hour 48, hour 72, day 30

    Multiple timepoints will be compared to baseline between CsA and Placebo.

  2. Fold-change in Troponin plasma concentration

    Time frame: baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    The change of high-sensitive Troponin T will be compared to baseline between CsA and Placebo for multiple time points.

  3. Fold-change in creatine kinase plasma concentration

    Time frame: baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    The change of creatine kinase will be compared to baseline between CsA and Placebo for multiple time points.

  4. Fold-change in NTproBNP plasma concentration

    Time frame: baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    The change of NTproBNP will be compared to baseline between CsA and Placebo for multiple time points.

  5. Fold-change in interleukin-6 plasma concentration

    Time frame: baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    The change of interleukin-6 will be compared to baseline between CsA and Placebo for multiple time points.

  6. Fold-change in procalcitonin plasma concentration

    Time frame: baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

    The change of procalcitonin will be compared to baseline between CsA and Placebo for multiple time points.

  7. Myocardial edema

    Time frame: hour 72

    Cardiac MRI will be used to assess the T2 signal intensity ratio for comparison between CsA and Placebo at 72h.

  8. Myocardial inflammation

    Time frame: hour 72

    Cardiac MRI will be used to assess the early gadolinium enhancement ratio for comparison between CsA and Placebo at 72h.

  9. Rate of cardiovascular events at day 30

    Time frame: 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.

  10. Rate of cardiovascular events at 1 year

    Time frame: 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.

  11. Rate of novel disease onset

    Time frame: day 30 and at 1 year

    At 30 days and 1-year novel clinical diagnoses during follow-up including cancer or neurological diseases will be assessed.

  12. Symptom burden at day 30

    Time frame: 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).

  13. Symptom burden at 1 year

    Time frame: 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).

  14. Depression score at day 30

    Time frame: 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).

  15. Depression score at year 1

    Time frame: 1 year

    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).

  16. Anxiety score at day 30

    Time frame: 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).

  17. Anxiety score at year 1

    Time frame: 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).

  18. PTSD score at 30 days

    Time frame: day 30

    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).

  19. PTSD score at 1 year

    Time frame: year 1

    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).

  20. Length of intermediate care or intensive care unit stay

    Time frame: day 30

    Length of intermediate care or intensive care unit stay will be compared between groups

  21. Length of hospital stay

    Time frame: day 30

    Length of hospital stay will be compared between groups

Study contacts

Contact information is provided by the study sponsor or research team.

Bastian Bruns, MD

CONTACT

[email protected]

+496221-56-36266

Sponsors and collaborators

Lead sponsor

University Hospital Heidelberg

Other

Collaborators

  • Coordinating Centre for Clinical Studies (KKS) Heidelberg
  • German Centre of Cardiovascular Research (DZHK)

Registry information

Official study title

Cyclosporine In Takotsubo Syndrome (CIT) Trial

Acronym: CIT

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Jul 14, 2023
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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