Clinical trial • Phase II • Cardiology

CICLOSPORIN for Takotsubo syndrome

Phase II trial of CICLOSPORIN for Takotsubo syndrome.

Overview

Trial Therapeutic Area
Cardiology
Trial Disease
Takotsubo syndrome
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
20-06-2024
First CTIS Authorization Date
30-08-2024

Trial design

Randomised, placebo (sodium chloride) intravenous bolus matching csa schedule. intervention arm: cyclosporine a 2.5 mg/kg intravenous bolus given at t0, t12 and t24; comparator arm: placebo (sodium chloride) intravenous bolus given at t0, t12 and t24 (matching schedule).-controlled Phase II trial across 24 sites in Germany.

Randomised
Yes
Comparator
Placebo (Sodium chloride) intravenous bolus matching CsA schedule. Intervention arm: Cyclosporine A 2.5 mg/kg intravenous bolus given at T0, T12 and T24; Comparator arm: placebo (sodium chloride) intravenous bolus given at T0, T12 and T24 (matching schedule).
Target Sample Size
204
Trial Duration For Participant
365

Eligibility

Recruits 204 Vulnerable population selected. Written informed consent is required from participants (patients aged over 18). Multiple informed consent forms and procedures are provided in the documentation including forms for legal authorised representative (LAR), spouse, oral consent, independent doctor, DZHK Heart Bank consent and subsequent consent versions, indicating processes to obtain consent where participants may be incapacitated or require alternative consenting routes..

Pregnancy Exclusion
Female patients currently pregnant or women of childbearing age without negative pregnancy test or without effective contraception
Vulnerable Population
Vulnerable population selected. Written informed consent is required from participants (patients aged over 18). Multiple informed consent forms and procedures are provided in the documentation including forms for legal authorised representative (LAR), spouse, oral consent, independent doctor, DZHK Heart Bank consent and subsequent consent versions, indicating processes to obtain consent where participants may be incapacitated or require alternative consenting routes.

Inclusion criteria

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

Exclusion criteria

  • {"criterion_text":"- Acute coronary syndrome (ACS) with significant coronary stenosis potentially associated with wall motion abnormalities (WMA) or percutaneous coronary intervention (PCI)"}
  • {"criterion_text":"- History of chronic renal insufficiency (either creatinin clearance <30 ml/min/1.73m² or current medical care for severe renal insufficiency)"}
  • {"criterion_text":"- History of liver insufficiency"}
  • {"criterion_text":"- Uncontrolled hypertension at the time of screening for study inclusion (systolic blood pressure >180mmHg and/or diastolic blood pressure >110mmHg)"}
  • {"criterion_text":"- Current medication with any compound containing Hypericum perforatum (St. John’s worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine (Rosuvastatine > 5mg within 24h before IMP administration)"}
  • {"criterion_text":"- Female patients currently pregnant or women of childbearing age without negative pregnancy test or without effective contraception"}
  • {"criterion_text":"- Any disorder associated with immunological dysfunction ≤6 months prior to presentation (autoimmune disease, known positive serology for HIV or hepatitis)"}
  • {"criterion_text":"- Immunosuppressive, chemotherapeutical, or antibody treatment"}
  • {"criterion_text":"- Participation in other clinical trials except for non-interventional trials"}
  • {"criterion_text":"- Neither male nor female at birth"}
  • {"criterion_text":"- Infection (defined as concomitant infection with a positive blood culture at the time of study inclusion)"}
  • {"criterion_text":"- History of hypersensitivity to cyclosporine"}
  • {"criterion_text":"- History of hypersensitivity to egg, peanut or soybean proteins"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Primary efficacy endpoint: Reduction of myocardial damage quantified by AUC of centrally measured highsensitive cardiac Troponin T (TnT) over 72 h.","definition_or_measurement_approach":"Centrally measured high-sensitive Troponin T area under the curve (AUC) over 72 hours with measurements at baseline, 3h, 12h, 24h, 36h, 48h, 60h and 72h."}

Secondary endpoints

  • {"endpoint_text":"- Change in TnT/NTproBNP at T3/12/24/36/48/60/72/M1 and change in LVEF at T48/72/M1 (vs. baseline)","definition_or_measurement_approach":"Biomarker changes (TnT, NTproBNP) measured at specified timepoints (3h, 12h, 24h, 36h, 48h, 60h, 72h and Month1) and left ventricular ejection fraction (LVEF) assessed at 48h, 72h and Month1 vs baseline."}
  • {"endpoint_text":"- Myocardial edema/inflammation at T48-72 (cMRI, T2 SIand EGE ratio (lake louise criteria))","definition_or_measurement_approach":"Cardiac MRI at 48–72 hours assessing T2 signal intensity and early gadolinium enhancement (EGE) ratio according to Lake Louise criteria to evaluate myocardial edema/inflammation."}
  • {"endpoint_text":"- Length of stay on IMC/ICU and length of hospital stay","definition_or_measurement_approach":"Recorded duration of intermediate care/intensive care unit stay and total hospital length of stay."}
  • {"endpoint_text":"- Composite cardiovascular outcome at 30d and 1year: mortality from any cause, stroke, myocardial infarction, heart failure, hospitalization, recurrent TTS, cardiac arrest / ventricular fibrillation, ventricular tachycardia, novel atrial fibrillation, thromboembolism, LV-Thrombus, AV-Block, ventricular rupture and new onset atrial fibrillation","definition_or_measurement_approach":"Composite event rate assessed at 30 days and 1 year including the listed cardiovascular events and outcomes."}
  • {"endpoint_text":"- Psychosocial and quality of life assessments between groups at M1 vs. M12","definition_or_measurement_approach":"Validated psychosocial and quality-of-life instruments assessed at Month 1 and Month 12 comparing groups."}

Recruitment

Planned Sample Size
204
Recruitment Window Months
43
Consent Approach
Written informed consent from the participant is required. Multiple consent variants and supporting documents are provided (subject information and informed consent form, oral consent form, consent by independent doctor, LAR (legal authorised representative) consent, spouse consent, DZHK Heart Bank consent, subsequent consent versions), indicating procedures for obtaining consent where participants may be unable to consent themselves. Study population restricted to adults (>18 years). No languages explicitly listed in the available metadata.

Geography

Total Number Of Sites
24
Total Number Of Participants
204

Germany

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
04-12-2025
Processing Time Days
485
Number Of Sites
24
Number Of Participants
204

Sites

Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Division of Cardiology, Pneumology, and Vascular Diseases
Contact Person Name
Fabian Voß
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Medizinische Klinik und Poiliklinik der Inneren Medizin I, Studienzentrum Kardiologie
Contact Person Name
Karl-Ludwig Laugwitz
Contact Person Email
sabrina.doering@mri.tum.de
Site Name
Universitaetsklinikum Frankfurt AöR
Department Name
Med. Klinik 3 – Kardiologie, Angiologie
Contact Person Name
Maria Papathanasiou
Site Name
Rostock University Medical Center
Department Name
Department für Innere Medizin, Klinik und Poliklinik für Kardiologie
Contact Person Name
Hüseyin Ince
Site Name
Universitaetsklinikum Magdeburg AöR
Department Name
Klinik für Kardiologie und Angiologie
Contact Person Name
Rüdiger Braun-Dullaeus
Contact Person Email
r.braun.dullaeus@med.ovgu.de
Site Name
Universitaetsklinikum Mannheim GmbH
Department Name
Medizinische Klinik I
Contact Person Name
Ibrahim Akin
Contact Person Email
ibrahim.akin@umm.de
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Medizinische Klinik und Poliklinik II, Herzzentrum
Contact Person Name
Georg Nickenig
Contact Person Email
Georg.Nickenig@ukbonn.de
Site Name
Helios Universitaetsklinikum Wuppertal
Department Name
Kardiologie
Contact Person Name
Melchior Seyfarth
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Deutsches Herzzentrum der Charité, Klinik für Kardiologie, Angiologie und Intensivmedizin
Contact Person Name
Frank Edelmann
Contact Person Email
frank.edelmann@dhzc-charite.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Heart Center Göttingen
Contact Person Name
Stephan von Haehling
Site Name
Martin-Luther-Universitaet Halle-Wittenberg
Department Name
Universitätsklinik und Poliklinik für Innere Medizin III
Contact Person Name
Daniel Sedding
Site Name
Herzzentrum Leipzig GmbH
Department Name
Leipzig Heart Center
Contact Person Name
Holger Thiele
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Internal Medicine 3
Contact Person Name
Norbert Frey
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für Kardiologie, Angiologie und Intensivmedizin, Campus Benjamin Franklin
Contact Person Name
Christian Oeing
Site Name
Kerckhoff-Klinik GmbH
Department Name
Kardiologie
Contact Person Name
Samuel Sossalla
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Medizinische Klinik II, Universitäres Herzzentrum Lübeck
Contact Person Name
Ingo Eitel
Contact Person Email
Ingo.Eitel@uksh.de
Site Name
University Hospital Cologne AöR
Department Name
Herzzentrum der Universität zu Köln
Contact Person Name
Roman Pfister
Contact Person Email
roman.pfister@uk-koeln.de
Site Name
Herzzentrum Dresden GmbH Universitaetsklinik
Department Name
Klinik für Innere Medizin und Kardiologie
Contact Person Name
Stefanie Jellinghaus
Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Kardiologie
Contact Person Name
Rolf Wachter
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Department Name
Zentrum für Kardiologie
Contact Person Name
Maike Knorr
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin II
Contact Person Name
Wolfgang Rottbauer
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Klinik für Kardiologie
Contact Person Name
Christina Magnussen
Contact Person Email
c.magnussen@uke.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Kardiologie und Angiologie
Contact Person Name
Tienush Rassaf
Contact Person Email
tienush.rassaf@uk-essen.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik I, Standort Großhadern
Contact Person Name
Ludwig Weckbach

Sponsor

Primary sponsor

Full Name
Universitaetsklinikum Heidelberg AöR
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Germany

Third parties

  • {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"[1,10,12,5,6,8]","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
Sandimmun® 50 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Active Substance
CICLOSPORIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
Intravenous bolus
Authorisation Status
Authorised in Germany (marketing authorisation number 3123.00.00)
Starting Dose
2.5 mg/kg
Dose Levels
2.5 mg/kg (single planned dose per administration)
Frequency
At T0, T12 and T24 (three administrations)
Investigational Product Name
SODIUM CHLORIDE
Active Substance
SODIUM CHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
Intravenous bolus
Authorisation Status
Authorised / pharmaceutical aid (used as placebo/diluent)
Frequency
At T0, T12 and T24 (matching placebo schedule)

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