An interventional study of Cardiac Contractility Modulation (CCM) and CRT in Chagas Cardiomyopathy, Heart Failure and Systolic Dysfunction, sponsored by InCor Heart Institute. Recruiting at 1 site in Brazil. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by InCor Heart Institute · Not applicable, Interventional, and Treatment
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.
Chagas Disease:
Chagas disease (Trypanosomiasis Americana) is caused by the protozoan parasite Trypanosoma cruzi, which is transmitted to humans through the feces of a hematophagous insect (family Triatominae) in most cases. The infection usually occurs in childhood, and the acute phase has an incubation period of 1 to 2 weeks and can last up to 3 months. Then follows the chronic phase, in which for a long time - 2-4 decades most of the time - patients have only positive serology for Chagas disease (CD), without symptoms or other signs of clinically apparent disease.
Therefore, such patients present the so-called indeterminate form of Chagas disease, whose prognosis is essentially benign.
While due to pathogenic mechanisms still incompletely understood, many patients remain with this form of the disease for life around 30 to 50% of infected individuals evolve to certain forms like cardiac, digestive, or mixed. Chronic Chagas cardiomyopathy (CCC) has a hemodynamic pattern like dilated idiopathic cardiomyopathy but has marked pathophysiological peculiarities. The most common and most serious clinical form of CD is responsible for significant morbidity and mortality in many Latin countries -Americans (and with epidemiological relevance also contemporarily recognized in countries with immigration by individuals from those countries).
It is estimated that 8-10 million people are infected with Trypanosoma cruzi in Latin America and other countries. Considering the worst-case scenario, we can deduce that 3-5 million infected individuals will manifest clinical forms of the disease in its chronic phase.
The disease severity:
In addition to the criteria used in the risk stratification shown in Tables 1 and 2, several markers of worse prognosis have been identified by several authors, especially concerning sudden cardiac death in different clinical contexts.
Characteristics such: as presyncope and syncope; left ventricular dysfunction; heart failure; sustained ventricular tachycardia (VT) or non-sustained ventricular tachycardia; severe bradyarrhythmia (sinus node disease and advanced atrioventricular block); and previous cardiac arrest were identified as markers of risk of sudden cardiac death (SCD). On the other hand, isolated ventricular extrasystoles on Holter monitoring and right bundle-branch block do not significantly interfere with the prognosis of CCC. SCD is often associated with manifestations of heart failure (HF), but it can also occur in patients with asymptomatic left ventricular dysfunction. It accounts for approximately 55 to 65% of all causes of death, whereas refractory HF is a cause of death in about 25 to 30% of patients and systemic or pulmonary thromboembolism in about 10 to 15%. Indicador não definido. Very rarely, aneurysm rupture can be the mechanism of sudden death in CCC.
Recently, the correlation between CCC stages and causes of mortality has been schematically described. SCD usually affects patients from stage II of the disease onwards, being more relevant in stage III and a little less in stage IV, in which refractory heart failure as a cause of death becomes quite frequent.
Therapeutic Options for Heart Failure. As in other heart diseases, the treatment of HF in CCC is based on the routine use of a combination of three types of drugs: diuretics, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARB) and adrenergic beta-blockers (BB). However, despite CD representing an important cause of HF in Latin America, patients with CD and HF were not included in the large studies that validated those drugs to treat HF. Therefore, the real efficacy and tolerability of these drugs in patients with CCC have not been scientifically established, and their use is empirically extrapolated from the support obtained in HF of other etiologies.
In the same sense, the scientific evidence regarding the role of CRT in CCC is not supported by randomized studies. Furthermore, the low prevalence of left bundle block, an independent marker of CRT response, in CCC is a limiting factor for its indication of this therapeutic option. Some observational studies have been carried out to recognize other candidates for CRT in CCC, but the evidence is still poor.
Heart transplantation is a good option for severe cases, but its application is very limited by the low availability of donors.
Recently, an excellent adjunctive option was introduced, and tested in several heart diseases but not in patients with CCC. It is an implantable device capable of modulating myocardial contractility: Cardiac Contractility Modulation (CCM).
Cardiac Contractility Modulation:
CCM consists of high-tension stimulation of the right ventricular septum during the absolute refractory period, 30-40ms after cardiomyocyte activation. This stimulation acts on calcium currents and increases ventricular contractility and, as a consequence, improves functional capacity.
In a 2019 meta-analytic study, Mando R et al. evaluated four randomized studies that applied the CCM technique compared to optimized drug therapy. The authors concluded that, in short-term follow-up, there is health-related quality of life gains (as measured by the Minnesota questionnaire) and that these were significantly greater in patients treated with CCM. However, they did not observe significantly better results in the functional test evaluated by the 6-minute walk test, nor regarding mortality and hospitalization from any causes.
Abraham WT et al. performed an open-label randomized trial to evaluate the adjunctive effect of CCM therapy to optimized therapy in 160 patients with symptoms of HF functional class III or IV by NYHA classification, sinus rhythm, QRS duration \<130ms, and LVEF ≥25%, and ≤45%. Of these, 74 patients underwent CCM therapy for 24 weeks. The results indicated that CCM therapy is safe and improves exercise tolerance and quality of life. The composite endpoint of cardiovascular death and HF hospitalizations was also reduced and clinical effects were observed for the entire LVEF range studied. More specifically, superior clinical efficacy was observed in patients with LVEF between 35% and 45%. These data point in the direction that CCM may be an interesting adjuvant option in HF therapy.
Hypothesis:
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.
Objectives:
Primary objective - To assess the short-term impact on quality of life and myocardial contractility of an implantable electronic cardiac device for cardiac contractility modulation compared to CRT in patients with CCC, non-LBBB, and advanced HF.
Secondary objectives - To record the clinical evolution, including the need for hospitalization, the functional class according to the New York Heart Association, and the functional capacity of an implantable electronic cardiac device for cardiac contractility modulation compared to CRT, in patients with CCC, non-LBBB, and advanced HF.
17 studies on the registry are indexed under Chagas Cardiomyopathy; 2 are open to participants now.
This study's planned enrollment of 60 is above the median of 45 across 13 interventional studies indexed under Chagas Cardiomyopathy.
Browse Chagas Cardiomyopathy studies →InCor Heart Institute is the lead sponsor of 27 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CCM implantation.
Device: Cardiac Contractility Modulation (CCM)
CRT implantation
Device: CRT
Cardiac Contractility Modulation (CCM) implantation
Cardiac Resynchronization Therapy
QoL Score
KCCQS - Kansas City cardiomyopathy quality score
Time frame: At baseline
QoL Score
KCCQS - Kansas City cardiomyopathy quality score
Time frame: At 6 months
GLS
Global longitudinal strain at rest/effort - (tissue tracking)
Time frame: At baseline
GLS
Global longitudinal strain at rest/effort - (tissue tracking)
Time frame: At 6 months
6MWT
6-minute walk test
Time frame: At baseline
6MWT
6-minute walk test
Time frame: At 6 months
NYHAFC
HF functional class assessed as established by the NYHA
Time frame: At baseline
NYHAFC
HF functional class assessed as established by the NYHA
Time frame: At 6 months
LVEF
Left ventricle ejection fraction
Time frame: At baseline
LVEF
Left ventricle ejection fraction
Time frame: At 6 months
Heart Failure Hospitalization (HFH) checklist
Heart Failure Hospitalization
Time frame: Through study completion, an average of 6 months
Plan to share: No
Started May 2022 (actual). Primary completion is estimated for Dec 2027, 67 months after the start.
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