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Chagas DiseasePhase 4PARACHUTE-HFNCT04023227

Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC

A Phase 4 study testing Sacubitril/valsartan and Enalapril in people with Chagas Disease and Heart Failure, run by Novartis Pharmaceuticals at 79 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study was to evaluate the effect of sacubitril/valsartan 200 mg BID compared with enalapril 10 mg BID, in addition to conventional heart failure (HF) treatment, in improving a hierarchical composite of cardiovascular (CV) events (i.e. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Chagas Disease, Heart Failure
What is being tested?
Sacubitril/valsartan and Enalapril
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
922 participants
Where
79 sitesin 4 countries
Study dates
10 Dec 2019to 31 Mar 2025
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female ≥ 18 years of age
  • Diagnosis of NYHA Class II-IV HFrEF established by:
  • LVEF ≤ 40% within 12 months prior to Visit 1 made by any local measurement using echocardiography, multiple gated acquisition scan (MUGA), computerized tomography (CT) scanning, magnetic resonance imaging (MRI), or ventricular angiography, provided no subsequent measurement above 40% AND
  • NT-proBNP ≥ 600 pg/mL (or BNP ≥ 150 pg/mL) at Visit 1 OR
  • NT-proBNP ≥ 400 pg/mL (or BNP ≥ 100 pg/mL) at Visit 1 and a hospitalization for HF within the last 12 months
  • Chagas' disease diagnosis confirmed by at least two different serological tests for anti-Trypanosoma cruzi based on different principles or with different antigenic preparations, such as: enzyme-linked immunosorbent assay [ELISA], indirect immunofluorescence [IFI], indirect hemagglutination [IHA], western blot (WB), chemiluminescent immunoassay (CLIA). If documented history is not available, the tests may be performed during the screening

Who cannot join

  • Patients with history of suspected or proven angioedema or unable to tolerate ACEIs, ARBs or ARNI (e.g., due to cough, hypotension, renal dysfunction, hyperkalemia)
  • Use of sacubitril/valsartan in the past 3 months
  • Patients requiring continuous intravenous inotropic therapy or with indication of advanced support intervention for HF:
  • already on list for a heart transplantation
  • with current indication of left ventricular assist device, or cardiac resynchronization therapy (CRT)
  • Systemic systolic blood pressure lower than 95 mmHg or symptomatic hypotension
Show all 20Show fewer
  • Serum potassium > 5.2 mmol/L
  • Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 of body surface area
  • Severe gastrointestinal form of chronic Chagas' disease (demonstrated megaesophagus and/or important megacolon, e.g.: with compromised oral intake or surgical indication).
  • Clinical conditions or systemic diseases limiting proper patient participation
  • Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception
  • Presence of other cardiac conditions:
  • Previous cardiac surgery
  • Heart failure where, in the Investigator's judgement, there is a possible alternative primary etiology e.g., due to coronary artery disease, valve disease, congenital heart disease or other causes.
  • Untreated arrhythmia or serious conduction disease e.g., bradyarrhythmias, atrial fibrillation with rapid ventricular response, second or third degree atrioventricular block, etc.
  • Primary uncorrected valvar pathology like moderate to severe aortic stenosis, mitral stenosis and primary mitral regurgitation
  • Planned organ transplantation (or in listing for transplantation), planned cardiac or other major surgery (including ventricular assist device implantation)
  • History of malignancy of any organ system within the past 5 years.
  • Current confirmed COVID19 infection
  • Past COVID19 infection with persistent symptom burden suspected due to COVID19 (persistent symptoms may include, but are not limited to, continued cough, breathing difficulty, muscle/joint aches, and gastrointestinal symptoms from the time of COVID19 infection onward)

Trial locations and contacts

79 sites in 4 countries.

79 sites in 4 countries

Brazil45 sites

  • Novartis Investigative Site

    Belém, Pará, 66087-660

  • Novartis Investigative Site

    Belo Horizonte, Minas Gerais, 30130-100

  • Novartis Investigative Site

    Belo Horizonte, Minas Gerais, 30140 062

  • Novartis Investigative Site

    Belo Horizonte, Minas Gerais, 30150-270

  • Novartis Investigative Site

    Botucatu, São Paulo, 3880-1001

  • Novartis Investigative Site

    Bragança Paulista, São Paulo, 13183-091

  • Novartis Investigative Site

    Brasila, Federal District, 70673623

  • Novartis Investigative Site

    Brasília, Federal District, 70390-700

  • Novartis Investigative Site

    Brasília, Federal District, 70673-416

  • Novartis Investigative Site

    Campinas, São Paulo, 13020-431

  • Novartis Investigative Site

    Campinas, São Paulo, 13060 080

  • Novartis Investigative Site

    Campinas, São Paulo, 13060-904

  • Novartis Investigative Site

    Fortaleza, Ceará, 60125-025

  • Novartis Investigative Site

    Fortaleza, Ceará, 60430 370

  • Novartis Investigative Site

    Goiânia, Goiás, 74223-060

  • Novartis Investigative Site

    Goiânia, Goiás, 74223-130

  • Novartis Investigative Site

    Goiânia, Goiás, 74605-020

  • Novartis Investigative Site

    Ijuí, Rio Grande do Sul, 98700-000

  • Novartis Investigative Site

    Indaiatuba, São Paulo, 13330-570

  • Novartis Investigative Site

    Londrina, Paraná, 86038-440

  • Novartis Investigative Site

    Marília, São Paulo, 17515-000

  • Novartis Investigative Site

    Montes Claros, Minas Gerais, 39401-001

  • Novartis Investigative Site

    Passos, Minas Gerais, 37904-020

  • Novartis Investigative Site

    Recife, Pernambuco, 50100-060

  • Novartis Investigative Site

    Ribeirão Preto, São Paulo, 14010-190

  • Novartis Investigative Site

    Ribeirão Preto, São Paulo, 14048-900

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 20551-030

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 22240-006

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 40050-410

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 40110060

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 40323-010

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 41253-190

  • Novartis Investigative Site

    Santo André, São Paulo, 09080-001

  • Novartis Investigative Site

    Sao Jose Rio Preto, São Paulo, 15090-000

  • Novartis Investigative Site

    São Luís, Maranhão, 65020-070

  • Novartis Investigative Site

    São Paulo, São Paulo, 04012 909

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403-000

  • Novartis Investigative Site

    São Paulo, 05403-000

  • Novartis Investigative Site

    São Paulo, 15015-210

  • Novartis Investigative Site

    Tatuí, São Paulo, 18270-170

  • Novartis Investigative Site

    Teresina, Piauí, 64001-380

  • Novartis Investigative Site

    Uberaba, Minas Gerais, 38025-440

  • Novartis Investigative Site

    Uberlândia, Minas Gerais, 38400 500

  • Novartis Investigative Site

    Uberlândia, Minas Gerais, 38400-328

  • Novartis Investigative Site

    Votuporanga, São Paulo, 15500 003

Other trials in Brazil

Argentina24 sites

  • Novartis Investigative Site

    Buenos Aires, C1155 AHD

  • Novartis Investigative Site

    CABA, Buenos Aires, C1221ADC

  • Novartis Investigative Site

    CABA, Buenos Aires, C1425BEI

  • Novartis Investigative Site

    Córdoba, 5000

  • Novartis Investigative Site

    Córdoba, X5003DCE

  • Novartis Investigative Site

    Córdoba, X5004BAL

  • Novartis Investigative Site

    Córdoba, X5006CBI

  • Novartis Investigative Site

    Corrientes, W3400CDS

  • Novartis Investigative Site

    Formosa, P3600

  • Novartis Investigative Site

    Formosa, P3634XAR

  • Novartis Investigative Site

    Mendoza, M5500CHC

  • Novartis Investigative Site

    Ramos Mejía, Buenos Aires, B1704ETD

  • Novartis Investigative Site

    Rosario, Santa Fe Province, 2000

  • Novartis Investigative Site

    Rosario, Santa Fe Province, S2000DIF

  • Novartis Investigative Site

    Salta, Salta Province, A4406BPF

  • Novartis Investigative Site

    San Martín, Buenos Aires, 1604

  • Novartis Investigative Site

    San Miguel de Tucumán, San Miguel de Tucuman, T4000ICL

  • Novartis Investigative Site

    San Miguel Tucuman, Tucumán Province, T4000IFL

  • Novartis Investigative Site

    San Miguel Tucuman, Tucumán Province, T4000JCU

  • Novartis Investigative Site

    Santa Fe, S3000EOZ

  • Novartis Investigative Site

    Santa Fe, S3000FWO

  • Novartis Investigative Site

    Santiago del Estero, G4200AQK

  • Novartis Investigative Site

    Temperley, Buenos Aires, 1834

  • Novartis Investigative Site

    Villa María, Córdoba Province, X5900JKA

Other trials in Argentina

Colombia6 sites

  • Novartis Investigative Site

    Bogota, Cundinamarca, 110121

  • Novartis Investigative Site

    Bogota DC, 110111

  • Novartis Investigative Site

    Florida Blanca, 681001

  • Novartis Investigative Site

    Floridablanca, 681004

  • Novartis Investigative Site

    San Gil, Santander Department, 684031

  • Novartis Investigative Site

    Santa Marta, Magdalena Department, 30360

Other trials in Colombia

Mexico4 sites

  • Novartis Investigative Site

    Ciudad de, 14080

  • Novartis Investigative Site

    Mérida, Yucatán, 97000

  • Novartis Investigative Site

    Oaxaca City, 68000

  • Novartis Investigative Site

    Xalapa, 91193

Other trials in Mexico

About this study

Official title: A Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint, Phase 4 Study to Evaluate the Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With Chronic Chagas' Cardiomyopathy. The Study is Also Know as Prevention And Reduction of Adverse Outcomes in Chagasic Heart failUre Trial Evaluation (PARACHUTE-HF).

The purpose of this study was to evaluate the effect of sacubitril/valsartan 200 mg BID compared with enalapril 10 mg BID, in addition to conventional heart failure (HF) treatment, in improving a hierarchical composite of cardiovascular (CV) events (i.e. CV death or the occurrence of first HF hospitalization) and causing a greater reduction in n terminal prohormone of brain natriuretic peptide (NT-proBNP, at Week 12 from Baseline) in participants with HF with reduced ejection fraction (HFrEF) caused by chronic Chagas' cardiomyopathy (CCC).

Read the detailed description

This was a multinational, multicenter, parallel-group, prospective, randomized, open-label, with blinded-endpoint adjudication, active-controlled study. The target projected sample size was approximately 900 participants (450 in each arm). It was estimated that approximately 1800 participants would be screened at sites in Latin America, including Argentina, Brazil, Colombia, and Mexico.

Participants who met the eligibility requirements were randomly assigned in a 1:1 ratio to receive sacubitril/valsartan (target dose of 200 mg twice daily) or enalapril (target dose of 10 mg twice daily), in addition to their usual therapy, stratified by country, using a central, concealed, web-based, automated randomization system. Both groups entered a titration period of 3 to 6 weeks, aiming to achieve the target dose of sacubitril/valsartan 200 mg twice daily or enalapril 10 mg twice daily. The study follow-up succeeded the titration period and was to last until a total number of 302 events was reached and all randomized participants had a minimum follow-up of 12 weeks.

Being tested
Sacubitril/valsartan, Enalapril
Keywords
Chagas' disease, heart failure, angiotensin receptor-neprilysin inhibitor, ARNI, ARB, ACEI, sacubitril/valsartan, enalapril
Medical subject headings
Chagas Disease, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sacubitril/valsartanDrug

    Also called LCZ696; Entresto; Vymada

    Participants randomized to sacubitril/valsartan who were previously treated with angiotensin-converting enzyme inhibitors (ACEIs) had a 36-hour washout prior to receiving oral treatment with 50, 100, or 200 mg, film-coated tablets.

  • EnalaprilDrug

    Also called Renitec

    Oral treatment with 5 or 10 mg tablets.

Study groups in NCT04023227
Study groupRoleWhat they receive
Sacubitril/valsartanExperimentalParticipants received 3 to 6 weeks of titrated dosing with sacubitril/valsartan to achieve the target dose of 200 mg twice daily.
Receives: Drug: Sacubitril/valsartan
EnalaprilActive comparatorParticipants received 3 to 6 weeks of titrated dosing with enalapril to achieve the target dose of 10 mg twice daily.
Receives: Drug: Enalapril

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hierarchical Composite Endpoint Composed of Time to Cardiovascular (CV) Death, Time to First Heart Failure (HF) Hospitalization, and Relative Change in NT-proBNP From Baseline to Week 12

    The primary efficacy endpoint was analyzed using the win ratio approach comparing every participant in the sacubitril/valsartan arm to every participant in the enalapril arm to determine a winner. A winner in the pair-wise comparison had a delayed time to the occurrence of CV death; if time to the occurrence of CV death was censored, a winner had a delayed time to the occurrence of first HF hospitalization event; if the times to both CV events were censored, a winner had a more favorable (less increase or more decrease) change in NT-proBNP between Baseline and Week 12. The estimated win ratio was defined as the total number of winners in the sacubitril/valsartan arm divided by the total number of winners in the enalapril arm. A win ratio >1 represents a favorable outcome for the study drug being assessed.

    Measured: Total follow-up time up to approximately 36 months

  2. Percentage of Participants Who Died From Cardiovascular Causes

    Measured: Total follow up time up to approximately 36 months

  3. Percentage of Participants With First Hospitalization for Worsening Heart Failure

    Measured: Total follow up time up to approximately 36 months

  4. Change From Baseline to Week 12 in NT-proBNP Levels

    Geometric mean factor change was derived from a linear regression model of log(NT-proBNP), adjusted for country and baseline value.

    Measured: Baseline to Week 12

Secondary outcomes (6)

  1. Percentage of Participants With First Hospitalization Due to Heart Failure or Death From Cardiovascular Causes

    Measured: From the date of randomization to the first occurrence (total follow up time up to approximately 36 months)

  2. Percentage of Participants Who Died From Any Cause

    Measured: From date of randomization until the date of death from any cause assessed up to the end of the study, up to approximately 36 months

  3. Number of Participants Who Had Sudden Death or Resuscitated Sudden Cardiac Arrest

    Measured: From date of randomization until the date of the sudden death or resuscitated sudden cardiac arrest assessed up to the end of the study, up to approximately 36 months

  4. Number of Participants Who Had Visits to an Emergency Room Due to Heart Failure (HF) Where Intravenous Therapy Was Required

    Measured: From the date of randomization up to end of study. Total follow up time up to approximately 36 months.

  5. Number of Days Alive and Out of the Hospital

    The duration of hospital-free survival within 1 year from randomization was summarized.

    Measured: From the date of randomization up to end of study. Total follow up time up to approximately 36 months.

  6. Number of Hospitalizations Due to Heart Failure (HF) or Death Due to Cardiovascular (CV) Causes (Recurrent Events)

    Measured: From the date of randomization up to end of study. Total follow up time up to approximately 36 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2019
  2. Study start10 Dec 2019
  3. Primary completion16 Mar 2025
  4. Study completion31 Mar 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a Phase 4, multinational, multicenter, parallel-group, prospective, randomized, open-label, blinded-endpoint adjudication, active-controlled study to demonstrate superiority of sacubitril/valsartan over enalapril in improving a composite of cardiovascular (CV) events (CV death or first heart failure \[HF\] hospitalization), or in causing greater reduction or lesser increase in NT-proBNP levels at Week 12 in participants with HFrEF caused by CCC.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
922 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04023227
Sponsor's protocol ID
CLCZ696B3302
Acronym
PARACHUTE-HF
Status last verified
Apr 2026
First submitted
10 Jul 2019
Last updated
11 May 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Publications

  • Lopes RD, Bocchi EA, Echeverria LE, Demacq C, de Barros E Silva PGM, Barbosa LM, Damiani L, Sayyed S, Yoshida LAF, Furtado RHM, Morillo CA, Kevorkian R, Ramires F, Bahit MC, Magana A, Chavez-Mendoza A, Miguel da Silva AH, Coelho da Silva A, Freitas AF Jr, Romano AA, Parneix A, Segura A, Franca CCB, Botta CE, de Barros E, Perna ER, Montenegro E, Quiroz Diaz FR, Feitosa-Filho GS, Severini GV, Molina I, Miranda JDSS, Sala J, Kerr Saraiva JF, Carbajales J, Maia LN, Santana Passos LC, Simoes MV, Moreira MDCV, Nunes MCP, Hernandes ME, Hominal M, Zarandon RS, Leon de la Fuente R, Aras R, Bazan SGZ, Luiz da Silva T Jr, Madrini V, de Oliveira WA Jr, Saporito WF, Gimpelewicz C, McMurray JJV; Prevention and Reduction of Adverse Outcomes in Chagasic Heart Failure Trial Evaluation (PARACHUTE-HF) Investigators. Sacubitril/Valsartan vs Enalapril in Heart Failure Due to Chagas Disease: An Open-Label, Multicenter Randomized Clinical Trial. JAMA. 2026 Jan 6;335(1):49-59. doi: 10.1001/jama.2025.19808.

    PubMed 41335448

  • Bocchi EA, Echeverria LE, Demacq C, de Barros E Silva PGM, Mazza Barbosa L, Chiang LM, Damiani L, Morillo CA, Kevorkian R, Ramires F, Bahit MC, Ferrari A, Chavez-Mendoza A, Magana-Serrano JA, McMurray JJV, Gimpelewicz C, Lopes RD; PARACHUTE-HF Investigators. Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy: Rationale and Design of the PARACHUTE-HF Trial. JACC Heart Fail. 2024 Aug;12(8):1473-1486. doi: 10.1016/j.jchf.2024.05.021.

    PubMed 39111953

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Sacubitril/valsartan and Enalapril in people with Chagas Disease and Heart Failure, run by Novartis Pharmaceuticals at 79 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 79 sites in Brazil, Argentina, Colombia, Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hierarchical Composite Endpoint Composed of Time to Cardiovascular (CV) Death, Time to First Heart Failure (HF) Hospitalization, and Relative Change in NT-proBNP From Baseline to Week 12 (time frame: Total follow-up time up to approximately 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04023227, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.

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