LEVOMEMS: Comparison of the effects of dobutamine and levosimendan in the current treatment of heart diseases.

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol LEVOMEMS

Overview

Sponsor-declared trial summary

Phase Phase III and Phase IV (Integrated)

Status Authorised, recruitment pending

Participants planned 10

Countries 1

Sites 1

Heart failure patients with depressed left ventricular ejection fraction

To assess the change in the pulmonary arterial pressure and the cardiac output with levosimendan or dobutamine

Key facts

Sponsor: Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial): 2024-12-03
Transition trial: Yes
Low-intervention: Yes
Rare-disease indication: No
Vulnerable population: No

External identifiers

EU CT number: 2024-519631-42-00
EudraCT number: 2022-002688-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the change in the pulmonary arterial pressure and the cardiac output with levosimendan or dobutamine

Secondary objectives 5

Evaluate rehospitalizations due to heart failure and mortality during the follow-up period.
Assess the impact on quality of life and functional capacity (6MWT).
Describe the evolution of biomarkers (CA125, ST2, TnT, NTProBNP).
Monitor the evolution of pulmonary congestion (B-lines on lung ultrasound).
Evaluate renal function deterioration (50% reduction in glomerular filtration rate or creatinine >3 mg/dl) or hypotension (systolic blood pressure <100 mmHg).

Conditions and MedDRA coding

Heart failure patients with depressed left ventricular ejection fraction

Version	Level	Code	Term	System organ class
20.0	LLT	10010684	Congestive heart failure	10007541
20.0	LLT	10019279	Heart failure	10007541
20.0	LLT	10010684	Congestive heart failure	10007541
20.0	LLT	10019279	Heart failure	10007541
20.0	LLT	10019284	Heart failure congestive	10007541
26.1	LLT	10024106	Left heart failure	10007541

Study design 2 periods

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Phase 1 The initial inotropic agent will be dobutamine for 72 hours or levosimendan for 24 hours, assigned randomly. A new infusion with the other inotropic agent will be performed after 6 weeks (or 4 weeks if required by clinical criteria). The treatments will be administered via infusion through a catheter. The dose will be 5 mcg/kg/min for dobutamine and 12.5 mg without a bolus for levosimendan, respectively.	Randomised Controlled	None		Arm A: DOBUTAMINA (72H) AND LEVOSIMENDAN (24 H) Arm B: LEVOSIMENDAN (24H) AND DOBUTAMINA (72H)
2	Phase 2 Treatment will begin at 6 weeks after the second round of Phase 1 (or at 4 weeks if required by clinical criteria). Three treatment modes will be established and randomly assigned over 3 consecutive periods: dobutamine for 72 hours every 4 weeks, levosimendan for 24 hours every 4 weeks, and levosimendan for 6 hours every 2 weeks. The dose to be administered in the latter group will be 6.25 mg without a bolus. Each treatment period will last 3 months. A one-week washout period will be carried out between each treatment period. If the duration of the hemodynamic effects observed in Phase 1 is shorter than 4 weeks, the treatment cycles in each period may be modified on an individualized basis. The treatment will be maintained.	Randomised Controlled	None		Arm A: Dobutmanina (72h/4 weeks) Arm B: Levosimendan 6h/2 weeks Arm C: Levosimendan 24h/4 weeks

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

Age> 18 years
FEVI <35% for echocardiography in the last 6 months
Functional class NYHA> III with functional impairment despite optimized treatment of HF and diuretic with admission or decompensation treated on an outpatient basis with diuretic in the last six months that motivate the implementation of the CardioMEMS device
Signing of informed consent

Exclusion criteria 4

Creatinine clearance <20 ml / min
Presión arterial sistólica <90 mmHg
Pregnant or fertile women (who are in the period between menorrhagia and menopause) without effective contraceptive coverage, or in breastfeeding
Hypersensitivity to the active ingredients or to any of the excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Pulmonary blood pressure measured in mmhg and cardiac output measured in l / min at 3 months

Secondary endpoints 7

Combined criteria for death or rehospitalization for heart failure at the beginning and end of each period
Scores observed in the EuroQoL-5D quality of life test at the beginning and end of each period.
Scores observed in the 6-minute test at the beginning and end of each period
CA125, ST2, TnT and NTProBNP levels at the beginning and end of each period.
Pulmonary congestion parameters by pulmonary ultrasound: B lines
Renal function parameters:% of glomerular filtrate or creatinine levels (mg / dl), hypotension (systolic blood pressure <100mmHg).
Adverse events resulting from the administration of the drug

Investigational products

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

Test 2

Levosimendan

SCP111822643 · ATC

Active substance: Levosimendan
Route of administration: INTRAVENOUS
Max daily dose: 12 Aµg/kg microgram(s)/kilogram
Max total dose: 336 Aµg/kg microgram(s)/kilogram
Max treatment duration: 4 Week(s)
Authorisation status: Authorised
ATC code: C01CX08 — LEVOSIMENDAN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dobutamine Hydrochloride

SCP19397707 · ATC

Active substance: Dobutamine Hydrochloride
Route of administration: INTRAVENOUS
Max daily dose: 5000 Aµg/ml microgram(s)/millilitre
Max total dose: 140000 Aµg/ml microgram(s)/millilitre
Max treatment duration: 4 Week(s)
Authorisation status: Authorised
ATC code: C01CA07 — DOBUTAMINE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol

Sponsor organisation: Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol
Address: Carretera De Can Ruti
City: Barcelona
Postcode: 08916
Country: Spain

Scientific contact point

Organisation: Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol
Contact name: Andrea Borrellas

Public contact point

Organisation: Instituto De Investigacion En Ciencias De La Salud Germans Trias I Pujol
Contact name: Andrea Borrellas

Locations

1 EU/EEA country · 1 investigational sites

By country

Country	MS status	Planned subjects	Sites
Spain	Authorised, recruitment pending	10	1
Rest of world	—	0	—

Investigational sites

Spain

1 site · Authorised, recruitment pending

Hospital Germans Trias I Pujol

Cardiology Service, Carretera Canyet 1a Planta, 08916, Badalona

Results and documents

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

Documents 6 files

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

Type	Title	Version
Protocol (for publication)	D1_Protocol 2024-519631-42-00	4
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Statement	1
Subject information and informed consent form (for publication)	L1_SIS and ICF adults	5
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_Dobutamina	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_Levosimendan	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_SPA 2024-519631-42-00	4

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-11-20	Spain	Acceptable 2024-12-03	2024-12-03