Cardiac Contractility Modulation in Chagas Heart Disease

NCT05519046 | Recruiting DMC

• 1 other identifier: 57563722.3.0000.0068
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Chagas disease is an endemic problem in Latin America, where millions of people are chronically infected with T. cruzi. Recently, it was assumed to have clinical and epidemiological relevance in several other countries due to migratory and globalizing social factors. CCC occurs in 30-50% of infected individuals, causing considerable morbidity/mortality rates. Heart failure is the most prevalent morbidity. While CRT and drug treatment have been advocated and implemented without much success to improve the clinical condition of patients with CCC, there is no consistent scientific evidence on the role of cardiac contractility modulation (CCM) as a form of adjuvant treatment for heart failure in patients with CCC. The hypothesis of this study is that patients with CCC, advanced heart failure, severe systolic dysfunction, and non-LBB have better clinical and functional responses when undergoing implantation of a CCM device than when undergoing cardiac resynchronization therapy.

Conditions

Chagas Cardiomyopathy; Heart Failure; Systolic Dysfunction; Right Bundle Branch Block and Left Anterior Fascicular Block; Right Bundle Branch Block and Left Posterior Fascicular Block

Outcome Measures

Primary Outcomes (4)

• QoL Score

  KCCQS - Kansas City cardiomyopathy quality score

  At baseline

• QoL Score

  KCCQS - Kansas City cardiomyopathy quality score

  At 6 months

• GLS

  Global longitudinal strain at rest/effort - (tissue tracking)

  At baseline

• GLS

  Global longitudinal strain at rest/effort - (tissue tracking)

  At 6 months

Secondary Outcomes (7)

• 6MWT

  At baseline

• 6MWT

  At 6 months

• NYHAFC

  At baseline

• NYHAFC

  At 6 months

• LVEF

  At baseline

Study Arms (2)

Cardiac Contractility Modulation Group - CCM Group

EXPERIMENTAL

CCM implantation.

Device: Cardiac Contractility Modulation (CCM)

Cardiac Resynchronization Therapy Group - CRT Group

ACTIVE COMPARATOR

CRT implantation

Device: CRT

Interventions

Cardiac Contractility Modulation (CCM) DEVICE

Cardiac Contractility Modulation (CCM) implantation

Cardiac Contractility Modulation Group - CCM Group

CRT DEVICE

Cardiac Resynchronization Therapy

Cardiac Resynchronization Therapy Group - CRT Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signing of an informed consent form (ICF) before randomization and any study procedure,
• Both genders, age \>18 years and \<75 years,
• Recent positive (last two years) and documented serology for Chagas disease, in at least two different tests (indirect hemagglutination, indirect immunofluorescence, or ELISA),
• NYHA II-III heart failure functional class,
• LVEF\< 35%,
• Non left bundle branch block
• Intraventricular desynchrony (Yu index)
• Global longitudinal strain \>11 %.

You may not qualify if:

• Participation in another study, presently or terminated \<1 year ago, except for a totally unrelated observational study,
• Other concomitant cardiovascular diseases, including uncontrolled diabetes mellitus (systemic arterial hypertension without permitted target organ compromise),
• Kidney dysfunction (serum creatinine \>1.5mg/dL or eGFR \<30mL/min/1.73m2) or liver dysfunction, with diagnosis of cirrhosis or portal hypertension or elevated serum enzymes (AST or ALT) \> 3x the upper limit of normality,
• Moderate or severe chronic obstructive pulmonary disease,
• Peripheral polyneuropathy,
• Hyperthyroidism,
• Current alcoholism or not abandoned for \>2 years,
• Diagnosed with psychopathy or psychosis or addiction to illicit drugs,
• Life expectancy \<1 year, due to the disease itself or comorbidities (including NYHA class IV),
• Pregnancy or breastfeeding,
• Potential to become pregnant during the study (non-menopausal patients who have not undergone a radical and safe contraceptive process),
• Previously withdrawn from this study.

Sponsors & Collaborators

• InCor Heart Institute: lead
• Impulse Dynamics: collaborator
• I2medi Comercial Medica LTDA: collaborator

Study Sites (1)

InCor - HCFMUSP

São Paulo, São Paulo, 05403-900, Brazil

RECRUITING

Related Publications (32)

• Dias JC, Kloetzel K. The prognostic value of the electrocardiographic features of chronic Chagas' disease. Rev Inst Med Trop Sao Paulo. 1968 May-Jun;10(3):158-62. No abstract available.

  PMID: 4982469 BACKGROUND

• Espinosa R, Carrasco HA, Belandria F, Fuenmayor AM, Molina C, Gonzalez R, Martinez O. Life expectancy analysis in patients with Chagas' disease: prognosis after one decade (1973-1983). Int J Cardiol. 1985 May;8(1):45-56. doi: 10.1016/0167-5273(85)90262-1.

  PMID: 3997291 BACKGROUND

• Carrasco HA, Parada H, Guerrero L, Duque M, Duran D, Molina C. Prognostic implications of clinical, electrocardiographic and hemodynamic findings in chronic Chagas' disease. Int J Cardiol. 1994 Jan;43(1):27-38. doi: 10.1016/0167-5273(94)90087-6.

  PMID: 8175216 BACKGROUND

• Martinelli Filho M, Sosa E, Nishioka S, Scanavacca M, Bellotti G, Pileggi F. Clinical and electrophysiologic features of syncope in chronic chagasic heart disease. J Cardiovasc Electrophysiol. 1994 Jul;5(7):563-70. doi: 10.1111/j.1540-8167.1994.tb01297.x.

  PMID: 7987526 BACKGROUND

• Mady C, Cardoso RH, Barretto AC, da Luz PL, Bellotti G, Pileggi F. Survival and predictors of survival in patients with congestive heart failure due to Chagas' cardiomyopathy. Circulation. 1994 Dec;90(6):3098-102. doi: 10.1161/01.cir.90.6.3098.

  PMID: 7994859 BACKGROUND

• Bestetti RB, Dalbo CM, Freitas OC, Teno LA, Castilho OT, Oliveira JS. Noninvasive predictors of mortality for patients with Chagas' heart disease: a multivariate stepwise logistic regression study. Cardiology. 1994;84(4-5):261-7. doi: 10.1159/000176409.

  PMID: 8187110 BACKGROUND

• de Paola AA, Gomes JA, Terzian AB, Miyamoto MH, Martinez Fo EE. Ventricular tachycardia during exercise testing as a predictor of sudden death in patients with chronic chagasic cardiomyopathy and ventricular arrhythmias. Br Heart J. 1995 Sep;74(3):293-5. doi: 10.1136/hrt.74.3.293.

  PMID: 7547025 BACKGROUND

• Bestetti RB, Dalbo CM, Arruda CA, Correia Filho D, Freitas OC. Predictors of sudden cardiac death for patients with Chagas' disease: a hospital-derived cohort study. Cardiology. 1996 Nov-Dec;87(6):481-7. doi: 10.1159/000177142.

  PMID: 8904674 BACKGROUND

• Carrasco HA, Guerrero L, Parada H, Molina C, Vegas E, Chuecos R. Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients. Int J Cardiol. 1990 Jul;28(1):35-41. doi: 10.1016/0167-5273(90)90006-q.

  PMID: 2365530 BACKGROUND

• Lopes ER. Sudden death in patients with Chagas disease. Mem Inst Oswaldo Cruz. 1999;94 Suppl 1:321-4. doi: 10.1590/s0074-02761999000700061. No abstract available.

  PMID: 10677747 BACKGROUND

• Rassi A Jr, Rassi SG, Rassi A. Sudden death in Chagas' disease. Arq Bras Cardiol. 2001 Jan;76(1):75-96. doi: 10.1590/s0066-782x2001000100008. No abstract available. English, Portuguese.

  PMID: 11175486 BACKGROUND

• Bestetti R. Stroke in a hospital-derived cohort of patients with chronic Chagas' disease. Acta Cardiol. 2000 Feb;55(1):33-8. doi: 10.2143/AC.55.1.2005715.

  PMID: 10707756 BACKGROUND

• Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is independently associated with ischemic stroke in Chagas disease. Stroke. 2005 May;36(5):965-70. doi: 10.1161/01.STR.0000163104.92943.50. Epub 2005 Apr 21.

  PMID: 15845889 BACKGROUND

• Sousa AS, Xavier SS, Freitas GR, Hasslocher-Moreno A. Prevention strategies of cardioembolic ischemic stroke in Chagas' disease. Arq Bras Cardiol. 2008 Nov;91(5):306-10. doi: 10.1590/s0066-782x2008001700004. English, Portuguese.

  PMID: 19142374 BACKGROUND

• Oliveira JS, Barbieri Neto J. [Chagasic cardiopathy. Rupture of the apical aneurysm]. Arq Bras Cardiol. 1970 Oct;23(5):335-8. No abstract available. Portuguese.

  PMID: 4994717 BACKGROUND

• Pinto Dias JC. [Natural history of Chagas disease]. Arq Bras Cardiol. 1995 Oct;65(4):359-66. No abstract available. Portuguese.

  PMID: 8728813 BACKGROUND

• Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010 Apr 17;375(9723):1388-402. doi: 10.1016/S0140-6736(10)60061-X.

  PMID: 20399979 BACKGROUND

• Dias JC. The indeterminate form of human chronic Chagas' disease A clinical epidemiological review. Rev Soc Bras Med Trop. 1989 Jul-Sep;22(3):147-56. doi: 10.1590/s0037-86821989000300007.

  PMID: 2486527 BACKGROUND

• Barretto AC, Ianni BM. The undetermined form of Chagas' heart disease: concept and forensic implications. Sao Paulo Med J. 1995 Mar-Apr;113(2):797-801. doi: 10.1590/s1516-31801995000200010.

  PMID: 8650479 BACKGROUND

• Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV. Pathogenesis of chronic Chagas heart disease. Circulation. 2007 Mar 6;115(9):1109-23. doi: 10.1161/CIRCULATIONAHA.106.624296.

  PMID: 17339569 BACKGROUND

• Schmunis GA. Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Mem Inst Oswaldo Cruz. 2007 Oct 30;102 Suppl 1:75-85. doi: 10.1590/s0074-02762007005000093.

  PMID: 17891282 BACKGROUND

• Dias JC, Prata A, Correia D. Problems and perspectives for Chagas disease control: in search of a realistic analysis. Rev Soc Bras Med Trop. 2008 Mar-Apr;41(2):193-6. doi: 10.1590/s0037-86822008000200012.

  PMID: 18545843 BACKGROUND

• Moncayo A, Silveira AC. Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy. Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:17-30. doi: 10.1590/s0074-02762009000900005.

  PMID: 19753454 BACKGROUND

• Rassi A Jr, Dias JC, Marin-Neto JA, Rassi A. Challenges and opportunities for primary, secondary, and tertiary prevention of Chagas' disease. Heart. 2009 Apr;95(7):524-34. doi: 10.1136/hrt.2008.159624. Epub 2009 Jan 8.

  PMID: 19131444 BACKGROUND

• Rassi A Jr, Rassi A, Little WC, Xavier SS, Rassi SG, Rassi AG, Rassi GG, Hasslocher-Moreno A, Sousa AS, Scanavacca MI. Development and validation of a risk score for predicting death in Chagas' heart disease. N Engl J Med. 2006 Aug 24;355(8):799-808. doi: 10.1056/NEJMoa053241.

  PMID: 16928995 BACKGROUND

• Brunckhorst CB, Shemer I, Mika Y, Ben-Haim SA, Burkhoff D. Cardiac contractility modulation by non-excitatory currents: studies in isolated cardiac muscle. Eur J Heart Fail. 2006 Jan;8(1):7-15. doi: 10.1016/j.ejheart.2005.05.011. Epub 2005 Oct 3.

  PMID: 16202650 BACKGROUND

• Kahwash R, Burkhoff D, Abraham WT. Cardiac contractility modulation in patients with advanced heart failure. Expert Rev Cardiovasc Ther. 2013 May;11(5):635-45. doi: 10.1586/erc.13.48.

  PMID: 23621145 BACKGROUND

• Abi-Samra F, Gutterman D. Cardiac contractility modulation: a novel approach for the treatment of heart failure. Heart Fail Rev. 2016 Nov;21(6):645-660. doi: 10.1007/s10741-016-9571-6.

  PMID: 27394714 BACKGROUND

• Mando R, Goel A, Habash F, Saad M, Ayoub K, Vallurupalli S, Maskoun W. Outcomes of Cardiac Contractility Modulation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Cardiovasc Ther. 2019 Jun 17;2019:9769724. doi: 10.1155/2019/9769724. eCollection 2019.

  PMID: 31772622 BACKGROUND

• Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.

  PMID: 29754812 BACKGROUND

• Hinkle LE Jr, Thaler HT. Clinical classification of cardiac deaths. Circulation. 1982 Mar;65(3):457-64. doi: 10.1161/01.cir.65.3.457.

  PMID: 7055867 BACKGROUND

• Parissis JT, Nikolaou M, Farmakis D, Paraskevaidis IA, Bistola V, Venetsanou K, Katsaras D, Filippatos G, Kremastinos DT. Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure. Eur J Heart Fail. 2009 Feb;11(2):163-9. doi: 10.1093/eurjhf/hfn032.

  PMID: 19168514 BACKGROUND

MeSH Terms

Conditions

Chagas Cardiomyopathy; Heart Failure; Bundle-Branch Block

Condition Hierarchy (Ancestors)

Chagas Disease; Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Heart Block; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Martino Martinelli Filho, PhD

CONTACT

+551126615515; martino@incor.usp.br

Sergio F Siqueira, MsC

CONTACT

+551126615514; sergio.siqueira@hc.fm.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 29, 2022
• Study Start: May 25, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)