Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.

• ClinicalTrials.gov Identifier: NCT02033278
• Recruitment Status: Recruiting
• First Posted: January 10, 2014
• Last Update Posted: March 27, 2018
• Sponsor: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Collaborator: Iniciativa Andaluza en Terapias Avanzadas
• Information provided by (Responsible Party): Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

Tracking Information

• First Submitted Date: January 9, 2014
• First Posted Date: January 10, 2014
• Last Update Posted Date: March 27, 2018
• Actual Study Start Date: January 6, 2014
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 25, 2018): Changes in ventricular function measured angiographically. [ Time Frame: 24 months ]
• Original Primary Outcome Measures (submitted: January 9, 2014): Changes in ventricular function determined angiographically [ Time Frame: 12 months ]
• Change History: Complete list of historical versions of study NCT02033278 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 25, 2018)

• Degree of clinical improvement based on the absence of major cardiac events (MACE) during follow-up. [ Time Frame: 24 months ]
• Clinical and analytical progress (NYHA grade & BNP) [ Time Frame: 24 months ]
• Time of evolution since diagnosis of idiopathic dilated cardiomyopathy prior to study entry. [ Time Frame: 24 months ]
• Functional recovery as measured with ergometry [ Time Frame: 24 months ]
• Echocardiography and Electrocardiography variables [ Time Frame: 24 months ]

Original Secondary Outcome Measures (submitted: January 9, 2014)

• Degree of clinical improvement based on the absence of major cardiac events (MACE) during follow-up [ Time Frame: 12 months ]
• Presence or absence of symptoms or arrhythmias [ Time Frame: 12 months ]
• Evolution time since diagnosis of idiopathic dilated cardiomyopathy to the inclusion of the patient. [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
• Official Title: Multicenter Phase IIb Clinical Trial, Double-blind, Randomized, Controlled Placebo for to Assess the Efficacy of Intracoronary Infusion of Autologous Adult Stem Cells Mononuclear Marrow Unexpanded on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure.
• Brief Summary: Clinical trial phase IIb, double-blind, randomized, controlled with placebo. There is sufficient preliminary evidence to consider intracoronary injection of bone marrow progenitor cells as a viable, safe and beneficial treatment in patients with dilated cardiomyopathy, although the biological mechanism of action of bone marrow cells in the myocardium is not known. In this project we propose to investigate comparatively and from a biological and clinical point of view the applicability of regenerative therapy with autologous bone marrow cells in patients with dilated cardiomyopathy.

Detailed Description

The study population correspond to male and female patients with idiopathic dilated cardiomyopathy.

51 patients diagnosed with this disease are included. After inclusion, will proceed to the random allocation to study group or control group in a 2:1 ratio, 34 patients in the treatment group and 17 in the control group.

The total duration is expected to be 48 months: The inclusion period is 24 months and each patient assigned to the experimental group will be followed for 24 months, whereas that one ramdomized to the control group, will have a folow-up of 12 months. Upon completion there of, the patients will be followed in routine clinical practice.

This is a double blind study, in which all patients will perform the bone marrow harvesting.

All patients will receive the best medical treatment individualized (ACEIs or Angiotensin II receptor blocker, beta-blockers, diuretics and eplerenone) for at least 6 months prior to their participation in the clinical trial, so that the situation is stable and pharmacological basal condition is the same for everyone.

The bone marrow cells of patients assigned to placebo group will be cryopreserved, and once the trial is completed, the blind will be opened and all the patients who had been randomized to the control group, may be processed by the route of compassionate use with their own mononuclear bone marrow cells previously frozen.

The patients who are randomized to experimental group will be treated by the conventional treatment + infusion of autologous mononuclear bone marrow cells not expanded whereas the patients who are randomized to control group will be treated by the conventional treatment + infusion of placebo.

The main objective is to assess comparative the efficacy of intracoronary injection of bone marrow stem cells autologous to improve ventricular function in patients with idiopathic dilated cardiomyopathy who receive conventional medical treatment, compared with a control group who receive a infusion of placebo and conventional medical treatment. The improvement in ventricular function assessed by changes in angiographically determined ejection fraction.

Secondary objectives of the study are:

- 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.

The following parameters were evaluated: Functional class (NYHA), Natriuretic peptide B, Stress test (exercise time), Echocardiographic parameters of ventricular function, for example LVEF (%), TDV (ml), TSV (ml) and TAPSE (ms) and Biological parameters of cellular functionality, for example CD133 +, CD34 +, CD34 +/CD177 + and CD34 +/CD38- (in %).

- To determine, in the light of the obtained results, the application protocol suitable cell therapy for the treatment of dilated cardiomyopathy.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Idiopathic Dilated Cardiomyopathy

Intervention

• Drug: Infusion of autologous mononuclear bone marrow cells
  Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)
• Drug: Placebo infusion
  Placebo infusion plus conventional medical treatment (as indicated by clinician)

Study Arms

• Experimental: Infusion of autologous mononuclear bone marrow cells
  Infusion of autologous mononuclear bone marrow cells plus conventional medical treatment (as indicated by clinician)
  Intervention: Drug: Infusion of autologous mononuclear bone marrow cells
• Placebo Comparator: Placebo infusion
  Placebo infusion plus conventional medical treatment (as indicated by clinician)
  Intervention: Drug: Placebo infusion

• Publications *: Romero M, Suárez-de-Lezo J, Herrera C, Pan M, López-Aguilera J, Suárez-de-Lezo J Jr, Baeza-Garzón F, Hidalgo-Lesmes FJ, Fernández-López O, Martínez-Atienza J, Cebrián E, Martín-Palanco V, Jiménez-Moreno R, Gutiérrez-Fernández R, Nogueras S, Carmona MD, Ojeda S, Cuende N, Mata R. Randomised, double-blind, placebo-controlled clinical trial for evaluating the efficacy of intracoronary injection of autologous bone marrow mononuclear cells in the improvement of the ventricular function in patients with idiopathic dilated myocardiopathy: a study protocol. BMC Cardiovasc Disord. 2019 Aug 22;19(1):203. doi: 10.1186/s12872-019-1182-4.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 9, 2014): 51
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2022
• Estimated Primary Completion Date: February 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients of both sexes and ages between 18 and 70 years.
2. Patients diagnosed with dilated cardiomyopathy established by echocardiography.
3. Minimum evolution since diagnosis of 6 months.
4. Absence of coronary injury tested with multislice CT and/or hemodynamic study performed after study entry, or within the previous 36 months (or before in specific low risk clinical profiles) if no angina symptomatology is present.
5. Patients receiving optimized medical therapy for at least 6 months prior to enrollment (individually adjusted according to functional status).
6. Ejection fraction of the left ventricle <40% or ejection fraction of the left ventricle 40% -50% if left ventricular tele-diastolic volume is > 110 ml/m2.
7. Presence of sinus rhythm.
8. Writen informed consent for participation in the trial.
9. Normal laboratory parameters, defined by: Leukocytes ≥ 3000; Neutrophils ≥ 1500; Platelets ≥ 100,000; Aspartate aminotransferase / Alanine aminotransferase ≤ 2.5 standard range institution; Creatinine ≤ 2.5 mg / dL; Haemoglobin > 9 g/dL
10. Women of childbearing potential must have negative results on a pregnancy test and agree to use medically approved methods of contraception thoughout follow up.

Exclusion Criteria:

1. Secondary Dilated cardiomyopathy.
2. Recent history of myocarditis (< 6 months prior to study entry).
3. Patients amenable to receive cardiac resynchronization therapy
4. Patients in active waiting list for heart transplantation.
5. Coexistence of other serious systemic diseases.
6. Coexistence of any type of blood disease
7. Pregnant or breastfeeding women; or women of childbearing potential not comminting to use effective contraception.
8. Patients who are currently participating, or have completed their participation in a clinical trial within the last 3 months. Patients who have participated in any advanced therapies clinical trial any time previously.
9. Patients with malignant or pre-malignant tumors.
10. Positive serology for hepatitis B virus, hepatitis C virus or human immunodeficiency virus.
11. Use of any protocolo prohibited medication. A wash-out period of 2 months can be considered for inclusion in the trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Juliana Martínez-Atienza; 0034 955048278; juliana.martinez.ext@juntadeanlacia.es

• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02033278
• Other Study ID Numbers: CMMo/MD/2013
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Study Sponsor: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Collaborators: Iniciativa Andaluza en Terapias Avanzadas

Investigators

• Principal Investigator: Miguel Romero Moreno, MD, PhD; Hospital Universitario Reina Sofía
• Principal Investigator: Manuel Sobrino Marquez, MD; Hospitales Universitarios Virgen del Rocío
• Principal Investigator: Luis A Iñigo García, MD; Hospital Costa del Sol
• Principal Investigator: Ricardo Zayas Rueda, MD; Hospital Universitario Puerta del Mar
• Principal Investigator: Manuel De Mora Martín, MD, PhD; Hospital Regional U. Carlos Haya
• Principal Investigator: Silvia López Fernández, MD; University Hospital Virgen de las Nieves
• Principal Investigator: José Francisco Díaz Fernández, MD; Hospital Universitario Juan Ramón Jimenez
• Principal Investigator: Jesús Oneto Otero, MD; Hospital de Jerez
• Principal Investigator: Rafael Ruiz Salmerón, MD; Hospital Universitario Virgen Macarena

• PRS Account: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Verification Date: March 2018