ICH GCP - EU Clinical trials Registry - 2022-003628-42 (PL)

Stránka klinických studií Nct

Summary
EudraCT Number:	2022-003628-42
Sponsor's Protocol Code Number:	NBK182/1/2022
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-02-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2022-003628-42

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Levosimendan Therapy in low ejection fraction Takotsubo Syndrome (LevoTako Trial)

Randomizowane, podwójnie zaślepione, wieloośrodkowe badanie zastosowania lewozymendanu u pacjentów z zespołem Takotsubo i niską frakcją wyrzutową lewej komory (Badanie LevoTako)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of Levosimendan Therapy in low ejection fraction Takotsubo Syndrome

A.3.2

Name or abbreviated title of the trial where available

LevoTako

A.4.1

Sponsor's protocol code number

NBK182/1/2022

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medical University of Gdańsk
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical Research Agency
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Biuro „Centrum Wsparcia Badań Klinicznych Gdańskiego Uniwersytetu Medycznego”
B.5.2	Functional name of contact point	Piotr Widłak
B.5.3	Address:
B.5.3.1	Street Address	Skłodowskiej-Curie 3a
B.5.3.2	Town/ city	Gdańsk
B.5.3.3	Post code	80-210
B.5.3.4	Country	Poland
B.5.4	Telephone number	+4858349 18 85
B.5.6	E-mail	piotr.widlak@gumed.edu.pl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Simdax
D.2.1.1.2	Name of the Marketing Authorisation holder	Orion Corporation Orionintie 1 FI-02200 Espoo Finlandia
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Simdax
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Infusion (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Levosimendan
D.3.9.1	CAS number	141505-33-1
D.3.9.4	EV Substance Code	SUB08493MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Takotsubo syndrome (TTS), also known as apical ballooning syndrome, Takotsubo cardiomyopathy, broken heart syndrome, and stress-induced cardiomyopathy, is a rare condition and accounts for 1–3% of all patients referred to hemodynamic laboratories with a primary diagnosis of acute coronary syndrome (ACS).

E.1.1.1

Medical condition in easily understood language

Takotsubo syndrome

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10067676
E.1.2	Term	Takotsubo syndrome
E.1.2	System Organ Class	100000004849

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to assess whether the use of levosimendan in TTS improves LVEF in TTE 72 ± 3 hours after the end of the levosimendan infusion (primary primary endpoint).

E.2.2

Secondary objectives of the trial

Clinical benefit will be defined as a reduction in the incidence of adverse major cardiovascular events such as all-cause death, TTS recurrence or worsening heart failure leading to unscheduled hospitalization, stroke or TIA (major secondary endpoint) over the 12-month follow-up period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- 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

E.4

Principal exclusion criteria

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)
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.

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is to assess whether the use of levosimendan in TTS improves LVEF in TTE 72 ± 3 hours after the end of the levosimendan infusion (primary primary endpoint).

E.5.1.1

Timepoint(s) of evaluation of this end point

72 ± 3 hours after completion of the levosimendan infusion

E.5.2

Secondary end point(s)

Composite endpoint of 12-month all-cause mortality or proportion of major cardiovascular events (rehospitalization for recurrent TTS or heart failure, stroke or TIA, whichever comes first), all-cause mortality, re-hospitalization hospitalization due to recurrent TTS or heart failure, stroke or TIA, length of hospitalization, need for inotropic treatment, functional capacity (NYHA class), decrease in B-natriuretic peptide level.

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months (ongoing evaluation)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

170

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

190

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

in accordance with the therapeutic standard used in a given disease

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-03-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-19

P. End of Trial
P.	End of Trial Status	Ongoing

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