Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension

NCT ID: NCT05920005

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 702 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-22
• Study Completion Date: 2025-05-01

Brief Summary

This study will evaluate the safety and efficacy of a new combination of 3 (three) antihypertensive drugs in a single pill (candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg) compared with another combination of 3 (three) antihypertensive drugs (Exforge HCT® [valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg]). This will be a non-inferiority trial and the primary outcome will be blood pressure control after 12 weeks of treatment.

Detailed Description

This phase III, multicenter, randomized, double-blind, controlled, parallel trial will evaluate the non-inferiority of the association between candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg in relation to Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12 5mg + amlodipine 5mg) in the treatment of systemic arterial hypertension. A total of 698 participants will be included. Follow-up visits will occur four, eight, and twelve weeks after the date of the randomization visit. A telephone contact will be performed 30 days after the end of treatment. The primary efficacy outcome is the mean change in blood pressure, measured at the research site, 12 weeks after starting treatment, compared to baseline. Incidence of adverse events will be collected from the first dose of treatment up to 30 days after the end of the treatment foreseen in the protocol.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Association of candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg

The participant will take, once a day, 01 tablet of the active experimental drug (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg), plus 01 placebo, both orally.

Group Type: EXPERIMENTAL

candesartan cilexetil + chlorthalidone + amlodipine

Intervention Type: DRUG

Antihypertensive drugs in a single tablet (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg)

Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

The participant will take 01 tablet of Exforge HCT® active comparator (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg) plus 01 placebo, both orally.

Group Type: ACTIVE_COMPARATOR

Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

Intervention Type: DRUG

Antihypertensive drugs in a single tablet (association valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

Interventions

candesartan cilexetil + chlorthalidone + amlodipine

Antihypertensive drugs in a single tablet (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg)

Intervention Type: DRUG

Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

Antihypertensive drugs in a single tablet (association valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Both genders aged 18 years or older;
• Currently on dual antihypertensive therapy for at least 8 weeks, and non responders to that treatment, defined as measurements of SBP ≥ 140 mmHg and ≤180 mmHg and/or DBP≥90mmHg and ≤110 mmHg, assessed at the screening visit and randomization visit (both conditions are in accordance with the Brazilian Hypertension Guideline - 2020);
• Able to understand and consent to their participation in this clinical trial, manifested by signing the Informed Consent Form;

Exclusion Criteria

• Any significant clinical condition that, in the investigator's opinion, may interfere with participant safety;
• Any laboratory test finding that, in the investigator's opinion, may interfere with participant safety;
• Suspected or diagnosed with COVID 19;
• History of hypersensitivity to components of drugs used during the trial or to drugs derived from sulfonamides;
• Pregnant or breastfeeding women;
• Women in a reproductive age who do not agree to use contraceptive methods;
• Male participants who do not agree to use contraceptive methods;
• Participation in clinical trial protocols in the last 12 (twelve) months, unless the investigator judges that there may be a direct benefit to the participant;
• Participant who has some kind of relationship up to the second degree or bond with collaborators or employees of the Sponsor and the Research site;
• Estimated glomerular filtration rate (eGFR) less than 45 ml/min /1.73m2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) or end-stage renal disease;
• Severe liver dysfunction;
• Cardiogenic shock or reduced ejection fraction heart failure with a left ventricular ejection fraction less than or equal to 50%;
• Symptomatic congestive heart failure class II, III or IV, according to the New York Heart Association and/or participants with a history of infarction, unstable angina or cerebrovascular accident in the last 6 months prior to the beginning of the study;
• Clinically relevant ventricular cardiac arrhythmias;
• Obstructive coronary artery disease planning percutaneous or surgical intervention;
• Dementia syndrome;
• History of alcohol or illicit drug addiction in the six months prior to the date of signature of the Informed Consent Form;
• Obstructive biliary disorders;
• Refractory hypokalemia and/or conditions involving marked potassium loss, hyperkalemia (>5,5 mmol/L), and/or hyponatremia;
• History of symptomatic hyperuricemia;
• History of secondary hypertension;
• History of cancer, without documentation of remission/cure;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Libbs Farmacêutica LTDA

INDUSTRY

Sponsor Role: collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrícia Oliveira Guimarães, MD, PhD

Role: STUDY_DIRECTOR

Hospital Israelita Albert Einstein

Locations

Hospital de Urgência e Emergência de Rio Branco

Rio Branco, Acre, Brazil

Centro de Pesquisas Clinicas Dr. Marco Mota (Centro Universitario Cesmac/ Hospital do Coração de Alagoas)

Maceió, Alagoas, Brazil

Centro de Pesquisas em Diabetes e Doenças Endócrino Metabólicas LTDA

Fortaleza, Ceará, Brazil

Vitoria Clinical Research Institute LTDA

Vitória, Espírito Santo, Brazil

Santa Casa de Misericórdia de Passos

Passos, Minas Gerais, Brazil

Hospital Universitário Joao de Barros Barreto - UFPA

Belém, Pará, Brazil

Hospital 9 de Julho

São Paulo, Please Select, Brazil

Hospital Universitário Pedro Ernesto/UERJ

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto Atena de Pesquisa Clinica LTDA

Natal, Rio Grande do Norte, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda

Joinville, Santa Catarina, Brazil

Centro de Pesquisa Clínica do Coração

Aracaju, Sergipe, Brazil

Hospital Universitário São Francisco de Assis

Bragança Paulista, São Paulo, Brazil

Instituto de Pesquisa Clínica de Campinas

Campinas, São Paulo, Brazil

LOEMA - Instituto de Pesquisa Clinica & Consultores LTDA.

Campinas, São Paulo, Brazil

Indacor Serviços Médicos

Indaiatuba, São Paulo, Brazil

CIPES Centro Internacional de Pesquisa Clínica LTDA

São José dos Campos, São Paulo, Brazil

InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP

São Paulo, São Paulo, Brazil

Associação Lar São Francisco de Assis na Providência de Deus

São Paulo, São Paulo, Brazil

Hospital M'Boi Mirim

São Paulo, São Paulo, Brazil

Clínica Cardiológica

Votuporanga, São Paulo, Brazil

Santa Casa de Misericordia de Votuporanga

Votuporanga, São Paulo, Brazil

Countries

Brazil

References

Madrini V Jr, Tavares CAM, Albuquerque MTA, Silvestre OM, Felicio JS, Silveira FS, Hissa MN, Antunes MO, Mota-Gomes MA, Vidotti MH, Fuchs FD, Marcondes-Braga FG, Filho CRH, Troiani do Nascimento C, Bastos RA, Brandao AA, Cestario EES, Bortolotto LA, Castilho VC, Lapa MG, Magaton EAP, Fernandes PB, Albuquerque CSN, Silva LR, Berwanger O, Guimaraes PO. Efficacy and Safety of a Novel Triple Single-Pill For Uncontrolled Hypertension: the OPTION TREAT Trial. JACC Adv. 2025 Aug 25:102175. doi: 10.1016/j.jacadv.2025.102175. Online ahead of print.

Reference Type: DERIVED

PMID: 40892621 (View on PubMed)

Other Identifiers

LB2009

Identifier Type: -

Identifier Source: org_study_id