Cyclosporine In Takotsubo Syndrome

NCT05946772 | Recruiting Phase 2 DMC

• 1 other identifier: DZHK29
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 24

Brief 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.

Conditions

Takotsubo Cardiomyopathy

Keywords

Takotsubo syndrome; Troponin; Cyclosporine; Inflammation; Acute heart failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Change in Ejection fraction from baseline

  baseline, hour 24, hour 48, hour 72, day 30

• Fold-change in Troponin plasma concentration

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

• Fold-change in creatine kinase plasma concentration

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

• Fold-change in NTproBNP plasma concentration

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

• Fold-change in interleukin-6 plasma concentration

  baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

CsA

EXPERIMENTAL

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

Drug: Cyclosporine A

Interventions

Cyclosporine A DRUG

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

CsA

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Acute coronary syndrome (ACS) with significant coronary stenosis potentially associated with wall motion abnormalities (WMA) or percutaneous coronary intervention (PCI)
• 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
• 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

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• German Centre of Cardiovascular Research (DZHK): collaborator
• Coordinating Centre for Clinical Studies (KKS) Heidelberg: collaborator

Study Sites (24)

Kerckhoff Heart Center, Bad Nauheim / Gießen University

Bad Nauheim, Germany

RECRUITING

Department of Cardiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, Germany

RECRUITING

Department of Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum

Berlin, Germany

RECRUITING

Heart Centre - University Hospital Bonn

Bonn, Germany

RECRUITING

Department of Cardiology, University Hospital Köln

Cologne, Germany

RECRUITING

Department of Cardiology, University Hospital Dresden

Dresden, Germany

RECRUITING

Cardiovascular Centre - University Hospital Düsseldorf

Düsseldorf, Germany

RECRUITING

Department of Cardiology - University Hospital Essen

Essen, Germany

RECRUITING

Department of Cardiology, University Hospital Frankfurt

Frankfurt, Germany

RECRUITING

University Medical Center Göttingen

Göttingen, Germany

RECRUITING

Department of Cardiology, University Hospital Halle

Halle, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Department of Cardiology, Heidelberg University Hospital

Heidelberg, 69120, Germany

RECRUITING

Department of Cardiology, University Hospital Leipzig

Leipzig, Germany

RECRUITING

Leipzig Heart Center

Leipzig, Germany

RECRUITING

University Medical Center Schleswig-Holstein/Campus Lübeck

Lübeck, Germany

RECRUITING

Department of Cardiology, University Hospital Magdeburg

Magdeburg, Germany

RECRUITING

Department of Cardiology, University Hospital Mainz

Mainz, Germany

RECRUITING

Department of Cardiology, University Hospital Mannheim

Mannheim, Germany

RECRUITING

Department of Cardiology, Hospital of the Ludwig-Maximilians-University Munich

München, Germany

RECRUITING

University Hospital rechts der Isar, Technical University of Munich

München, Germany

RECRUITING

Department of Cardiology, University Hospital Rostock

Rostock, Germany

RECRUITING

Department of Cardiology, University Hospital Ulm

Ulm, Germany

RECRUITING

Department of Cardiology, University Hospital Wuppertal

Wuppertal, Germany

RECRUITING

Related Publications (1)

• Bruns B, Elsous N, Burghaus I, Steyrer K, Joos M, Kramer T, Scheffel M, Blankenberg S, Eitel I, Massberg S, Thiele H, Meder B, Backs J, Frey N. Rationale and design of the cyclosporine in Takotsubo syndrome (CIT) trial. Am Heart J. 2025 Nov;289:147-157. doi: 10.1016/j.ahj.2025.04.020. Epub 2025 Apr 21.

  PMID: 40268179 DERIVED

MeSH Terms

Conditions

Takotsubo Cardiomyopathy; Inflammation

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Norbert Frey, MD

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

• Bastian Bruns, MD

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bastian Bruns, MD

CONTACT

+496221-56-36266; bastian.bruns@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, care providers, and outcomes assessors are masked from study arm affiliation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. Norbert Frey, MD

Model Details: Double-blind multicentre RCT

Study Record Dates

• First Submitted: June 19, 2023
• First Posted: July 14, 2023
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (24)