Clinical trial to evaluate the efficacy of intracoronary infusion of autologous bone marrow mononuclear in patients with dilated cardiomyopathy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud, Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Dec 2013 → 23 Sep 2020

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516594-71-01

EudraCT number

2013-002015-98

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of intracoronary injection of autologous bone marrow mononucleated cells (BMMNCs) in improving ventricular function among patients with idiopathic dilated cardiomyopathy, for which there is currently no effective therapeutic alternative.

Secondary objectives 3

1. To analyze the predictors of good clinical response, functional and biological treatment with adult stem cells autologous mononuclear bone marrow not expanded in terms of functional recovery.
2. To determine, in view of the results obtained, the application protocol suitable cell therapy for the treatment of idiopathic MD, both in relation to the ideal characteristics of the bone marrow graft and the patients most likely to be beneficiaries of it, in order to establish a definitive strategy for including cell therapy in the standard treatment of MD of idiopathic origin in a near future if the results so advise.
3. To confirm product safety and the route of administration, as demonstrated in previous studies.

Conditions and MedDRA coding

Idiopathic dilated cardiomyopathy

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients of both sexes, aged between 18 and 70 years.
2. MD patients diagnosed with idiopathic established by echocardiography.
3. Minimum evolution from diagnosis of 6 months.
4. Absence of coronary lesions tested with multislice CT and / or hemodynamic study, obtained after patient inclusion, or 36 months before patient inclusion, provided that the patient has not presented anginal symptoms. In certain clinical profiles with very low risk of presenting coronary lesions, in order to avoid the risks of an invasive intervention or the use of ionizing radiation, the verification of this criterion can be based on tests performed within a longer period.
5. Patients with stable medical therapy for at least 6 months prior to enrollment (individually adjusted according to functional degree).
6. LVEF <40 % or LVEF 40 % -50 % if LVEDV > 110 ml/m2 measured by echocardiogram.
7. Presence of sinus rhythm.
8. Patients give their informed consent for participation in the clinical trial.
9. Normal laboratory parameters, defined by: WBC > 3000, Neutrophils >1500, Platelets > 100,000, AST / ALT < 2.5 standard range institution Creatinine < 2.5 mg / dl and Hemoglobin > 9 g/dl.
10. Women of childbearing age must obtain a negative pregnancy test at the time of inclusion in the study and agree to use a medically approved method of contraception while on study. Effective contraceptive method is defined as hormonal methods that inhibit ovulation (which combine estrogen with progestogen, or only progestogen) oral, transdermal, intravaginal, injectable or implantable, IUD, surgical sterilization or total abstinence.

Exclusion criteria 11

1. Dilated Cardiomyopathy Secondary.
2. Recent history of myocarditis in the 6 months prior to signing the informed consent.
3. Patients amenable to treatment with resynchronization. Those are patients with IC who have a QRS > 150, present symptoms and do not respond to drug treatment. Patients who have undergone a resynchronization within 6 months prior to inclusion, and who have not responded to it (have not changed the ejection fraction) is not excluded.
4. Patients in active waiting list for heart transplantation.
5. Coexistence of other serious systemic diseases.
6. Coexistence of any blood disease.
7. Pregnant women, lactating, or of childbearing age not using effective contraception.
8. Patients who are currently participating or have completed their participation in a clinical trial in less than 3 months or have participated in a clinical trial for Advanced Therapies (cell therapy, gene therapy or tissue engineering) at any time prior.
9. Patients with malignant or pre-malignant tumors.
10. Positive serology for HBV, HCV or HIV.
11. Patients at the time of study entry are taking any medications prohibited by the protocol. A “washout period” 2 months to be included in the trial is set.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in ventricular function determined angiographically.

Secondary endpoints 6

1. EFFICACY - PATIENT. Changes in the following parameters: Clinical evaluation and determination of NYHA functional class; Determination of BNP or NT fragment; Full echocardiogram; Assessment of functional capacity by exercise test without measurement of oxygen consumption; And cardiac catheterization.
2. EFFICACY - PATIENT. Evolution time from the diagnosis of idiopathic MD to the inclusion of the patient in the clinical trial.
3. EFFICACY - PATIENT. The degree of clinical improvement based on the absence of major cardiac events (MACE) during follow-up (severe arrhythmias, all cause death, cardiac death, cardiac hospitalization, inclusion in heart transplantation waiting list).
4. EFFICACY - PATIENT. The presence or absence of symptoms or arrhythmias and clinical functional degree. To this end, patients will be followed closely from a clinical point of view, with frequent telephone calls and periodic hospital check-ups on an outpatient basis.
5. EFFICACY - Laboratory of the cellular therapy medicinal product: Automatic cell counting to determine the total cellularity infused; Determination of the cellular composition in terms of the content of immature progenitors, endothelial line progenitors, mesenchymal line progenitors, expression of adhesion molecules, contamination of red blood cells in the cellular content and expression of the various membrane markers; Functional analysis of the chemotactic capacity of the infused cells.
6. SAFETY. Adverse events and Laboratory determinations: Cellular therapy medicinal product (microbiological cultivation) and Analytical determinations of blood count, plasma coagulation study and biochemistry on the patient.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Sponsor organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Address

Edificio S-2, Calle Americo Vespucio Nº 15, Parque Cientifico Y Tecnologico Cartuja 93 Calle Americo Vespucio Nº 15 Parque Cientifico Y Tecnologico Cartuja 93

City

Sevilla

Postcode

41092

Country

Spain

Scientific contact point

Organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Contact name

Gloria Carmona Sánchez

Public contact point

Organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Contact name

Blanca Quijano Ruiz

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Sponsor organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Address

Edificio S-2, Calle Americo Vespucio Nº 15, Parque Cientifico Y Tecnologico Cartuja 93 Calle Americo Vespucio Nº 15 Parque Cientifico Y Tecnologico Cartuja 93

City

Sevilla

Postcode

41092

Country

Spain

Locations

1 EU/EEA country · 9 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 4 files

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

Application history

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