Study of Levosimendan Therapy in low ejection fraction Takotsubo Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

22 Nov 2024 → 22 Dec 2025

Decision date (initial)

2024-12-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Medical Research Agency (Agencja Badań Medycznych)

External identifiers

EU CT number

2024-515060-32-00

EudraCT number

2022-003628-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate whether off-label use of levosimendan accelerates in-hospital left ventricular ejection fraction (LVEF) recovery and reduces the 12-month incidence of all-cause mortality or major adverse cardiovascular events (MACE) — including rehospitalization due to Takotsubo syndrome (TTS) recurrence or heart failure, stroke, or transient ischemic attack (TIA) — in patients with TTS and an LVEF ≤40% at admission, compared to placebo.

Secondary objectives 1

1. The secondary objective is to assess the composite endpoint, which includes the 12-month all-cause mortality or the rate of major adverse cardiovascular events (such as rehospitalization due to TTS recurrence or heart failure, stroke, or TIA, whichever occurs first). Other components of this objective include all-cause mortality, rehospitalization due to TTS recurrence or heart failure, stroke or TIA, length of hospitalization, the need for inotropic support, functional capacity as measured by NYHA class, and a decrease in B-natriuretic peptide levels. Since the trial's ultimate aim is to improve outcomes, the secondary objective specifically focuses on the 12-month all-cause mortality or the rate of major adverse cardiovascular events.

Conditions and MedDRA coding

Takotsubo syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Age > 60 years - Current hospitalization due to TTS - LVEF as assessed by echocardiography within 24 hours of admission ≤ 40% or decrease in LVEF by ≥ 10% compared to the last documented LVEF value before index hospitalization - NTproBNP concentration ≥ 500 pg/mL

Exclusion criteria 1

1. 1. Myocardial infarction within 30 days before randomization 2. Cerebrovascular disease (new stroke, subarachnoid hemorrhage) 3. Diagnosis of pheochromocytoma 4. Diagnosis of myocarditis 5. Low output syndrome - hypotonia with signs of tissue hypoperfusion (systolic blood pressure < 85 mmHg AND lactate > 2 mmol/L) XML File Identifier: oaQaRqf974zsAHLIB5CKhj434nk= Page 10/22 6. Pulmonary edema 7. Echocardiographic evidence of LVOTO 8. Uncontrolled hypertension 9. Planned revascularization or surgical treatment of heart failure within the next 12 months 10. Advanced chronic kidney disease (eGFR < 30 mL/min.) 11. Biochemical features of liver damage (>5 upper limits of reference hepatic aminotransferase activity and/or >3 upper limits of reference total bilirubin level) 12. Severe chronic lung disease with features of respiratory failure [defined as respiratory dysfunction impairing gas exchange and leading to hypoxemia - arterial blood oxygen partial pressure (PaO2) <60mmHg (8.0 kPa) and/or hypercapnia - increase in carbon dioxide partial pressure (PaCO2) ≥45mmHg (6, 0 kPa)] or severe spirometry abnormalities [defined as very severe obstruction, i.e., a decrease in the forced expiratory volume in 1 second (FEV1) <35% of normal value] or home oxygen therapy [in chronic lung disease with features of respiratory failure, indications for home oxygen therapy include: PaO2 ≤55 mmHg (corresponding to saturation ≤88%); PaO2 55-60 mmHg (corresponding to saturation ≤88%); and pulmonary hypertension, peripheral edema suggestive of right heart failure, or polycythemia (hematocrit>55%)]. 13. Concomitant chronic disease with poor prognosis (e.g., cancer) 14. Paroxysmal supraventricular tachycardia, paroxysmal ventricular tachycardia including torsade de pointes, severe atrioventricular block within one month before the study eligibility visit 15. History of hypersensitivity to levosimendan 16. Pregnancy or postpartum period 17. Patients with foreseeable problems cooperating with the medical and nursing team.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. In-hospital LVEF recovery

Secondary endpoints 1

1. Composite endpoint including 12-month all-cause mortality or major adverse cardiovascular events rate (rehospitalization due to TTS recurrence or heart failure, stroke or TIA, whatever occurs first)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Chief Medical Officer; Principal Investigator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Director of Clinical Research Support Centre

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications