Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension (OPTION TREAT)

A Multicenter, Double-blind, Controlled, Randomized Trial to Evaluate the Association Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: candesartan cilexetil + chlorthalidone + amlodipine; Drug: Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

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.

• Study Type: Interventional
• Enrollment (Actual): 702
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio De Janeiro, Brazil
    • Hospital Universitário Pedro Ernesto/UERJ
  • São Paulo, Brazil, 05403-900
    • InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
  • São Paulo, Brazil
    • Associação Lar São Francisco de Assis na Providência de Deus
  • AC
    • Rio Branco, AC, Brazil
      • Hospital de Urgência e Emergência de Rio Branco
  • Alagoas
    • Maceió, Alagoas, Brazil
      • Centro de Pesquisas Clinicas Dr. Marco Mota (Centro Universitario Cesmac/ Hospital do Coração de Alagoas)
  • Ceará
    • Fortaleza, Ceará, Brazil
      • Centro de Pesquisas em Diabetes e Doenças Endócrino Metabólicas LTDA
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil
      • Vitoria Clinical Research Institute LTDA
  • MG
    • Passos, MG, Brazil
      • Santa Casa de Misericordia de Passos
  • Pará
    • Belém, Pará, Brazil
      • Hospital Universitário João de Barros Barreto - UFPA
  • Please Select
    • Sao Paulo, Please Select, Brazil
      • Hospital 9 de Julho
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil
      • Instituto Atena de Pesquisa Clinica LTDA
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-007
      • Hospital de Clinicas de Porto Alegre
  • SE
    • Aracaju, SE, Brazil
      • Centro de Pesquisa Clínica do Coração
  • SP
    • Bragança Paulista, SP, Brazil
      • Hospital Universitário São Francisco de Assis
    • Campinas, SP, Brazil
      • Instituto de Pesquisa Clinica de Campinas
    • São Paulo, SP, Brazil
      • Hospital M'Boi Mirim
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil
      • CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
  • São Paulo
    • Campinas, São Paulo, Brazil
      • LOEMA - Instituto de Pesquisa Clinica & Consultores LTDA.
    • Indaiatuba, São Paulo, Brazil
      • Indacor Serviços Médicos
    • São José Dos Campos, São Paulo, Brazil
      • CIPES Centro Internacional de Pesquisa Clínica LTDA
    • Votuporanga, São Paulo, Brazil
      • Santa Casa de Misericórdia de Votuporanga
    • Votuporanga, São Paulo, Brazil
      • Clínica Cardiológica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: candesartan cilexetil + chlorthalidone + amlodipine; Antihypertensive drugs in a single tablet (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg)
Active Comparator: 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.	Drug: Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg); Antihypertensive drugs in a single tablet (association valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in systolic blood pressure (SBP)	The primary efficacy endpoint is the mean change in systolic blood pressure, measured at the site, 12 weeks after starting treatment, compared to baseline.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in diastolic blood pressure (DBP)	Variation in diastolic blood pressure 4, 6 and 12 weeks after starting treatment	12 weeks
Participants with blood pressure (SBP <140 and DBP<90 mmHg)	Proportion of participants who reach the target blood pressure (SBP <140 and DBP<90mmHg) 4, 8 and 12 weeks after starting treatment	12 weeks
Participants with SBP <120 mmHg	Proportion of participants who reach the target blood pressure of SBP <120 mmHg 4, 8 and 12 weeks after starting treatment	12 weeks
Participants with SBP <140 mmHg	Proportion of participants who reach target systolic blood pressure (SBP <140 mmHg) 4, 8 and 12 weeks after starting treatment	12 weeks
Participants with DBP<90 mmHg	Proportion of participants who reach the target diastolic blood pressure (DBP<90 mmHg) 4, 8 and 12 weeks after starting treatment	12 weeks
Participants with reduction greater than or equal to 20 mmHg in SBP	Proportion of participants who show a reduction greater than or equal to 20 mmHg in systolic blood pressure 4, 8 and 12 weeks after the start of treatment	12 weeks
Participants with reduction greater than or equal to 10 mmHg in DBP	Proportion of participants who have a reduction greater than or equal to 10 mmHg in diastolic blood pressure 4, 8 and 12 weeks after starting treatment	12 weeks

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Libbs Farmacêutica LTDA
• Investigators: Study Director: Patrícia Oliveira Guimarães, MD, PhD, Hospital Israelita Albert Einstein

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2023
• Primary Completion (Actual): March 31, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): June 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Calcium Channel Blockers; Vasodilator Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Valsartan; Amlodipine, Valsartan Drug Combination; Amlodipine; Hydrochlorothiazide; Chlorthalidone; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: LB2009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No