Cyclosporine In Takotsubo Syndrome (CIT)

University Hospital Heidelberg

Status and phase: Enrolling; Phase 2

Conditions: Takotsubo Cardiomyopathy

Treatments: Drug: Cyclosporine A; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05946772

DZHK29 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 204 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adult patients (age ≥ 18 years)

2. Symptom onset < 24h

3. With a high probability of TTS:

   1. InterTAK Diagnostic Score > 39 and
   2. Regional wall motion abnormality (WMA) consistent with TTS; no coronary intervention (PCI), or reperfused myocardial ischemia according to MRI

4. With a high probability of impaired outcome:

   1. InterTAK Prognostic Score >15 or
   2. GEIST Score > 19

Exclusion criteria

1. Suspected infection
2. Cardiac arrest, ventricular fibrillation, invasive ventilatory support
3. Known hypersensitivity to CsA, egg, peanut, or soya-bean proteins
4. Renal insufficiency (creatinin clearance < 30 ml/min/1.73m²)
5. Liver insufficiency
6. Uncontrolled hypertension (>180/110 mmHg)
7. Hypericum perforatum, Stiripentol, Aliskiren, Bosentan, or Rosuvastatin treatment
8. Pregnancy or women of childbearing age without contraception
9. Any disorder associated with immunological dysfunction < 6 months prior to presentation
10. Immunosuppressive therapy
11. Participation in another clinical trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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204 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

A concealed 0.9% sodium chloride (NaCl) preparation will be applied intravenously at baseline, 12h, and 24h.

Treatment:

Drug: Placebo

CsA

Experimental group

Description:

Cyclosporine A will be applied intravenously at baseline, 12h, and 24h.

Treatment:

Drug: Cyclosporine A