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: Recruiting
• 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 (Estimated): 698
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Vagner Madrini Junior, MD; Phone Number: +55 11 2151-5915; Email: vagner.junior@einstein.br
• Study Contact Backup: Name: Diogo Moia, MD; Phone Number: +55 11 2151-5915; Email: diogo.moia@einstein.br

Study Locations

• Brazil
  • Rio De Janeiro, Brazil
    • Not yet recruiting
    • Hospital Universitário Pedro Ernesto/UERJ
    • Contact: Andrea Araujo Brandão, MD
  • São Paulo, Brazil, 05403-900
    • Not yet recruiting
    • InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
    • Contact: Luiz A Bortolotto, MD, PhD; Phone Number: (11) 2661-5000; Email: luiz.bortolotto@incor.usp.br
  • São Paulo, Brazil
    • Not yet recruiting
    • Associação Lar São Francisco de Assis na Providência de Deus
    • Contact: Charlene Troiani do Nascimento
  • AC
    • Rio Branco, AC, Brazil
      • Not yet recruiting
      • Hospital de Urgência e Emergência de Rio Branco
      • Contact: Odilson Silvestre, MD-PhD
      • Principal Investigator: Odilson Silvestre
  • Alagoas
    • Maceió, Alagoas, Brazil
      • Not yet recruiting
      • Centro de Pesquisas Clinicas Dr. Marco Mota (Centro Universitario Cesmac/ Hospital do Coração de Alagoas)
      • Contact: Marco Antonio Mota Gomes, MD
  • Ceará
    • Fortaleza, Ceará, Brazil
      • Not yet recruiting
      • Centro de Pesquisas em Diabetes e Doenças Endócrino Metabólicas LTDA
      • Contact: Miguel Nasser Hissa
  • Espírito Santo
    • Vitória, Espírito Santo, Brazil
      • Not yet recruiting
      • Vitoria Clinical Research Institute LTDA
      • Contact: Priscilla Aquino Martins, MD
  • MG
    • Passos, MG, Brazil
      • Not yet recruiting
      • Santa Casa de Misericórdia de Passos
      • Contact: Walter Alvarenga, MD
  • Pará
    • Belém, Pará, Brazil
      • Not yet recruiting
      • Hospital Universitário João de Barros Barreto - UFPA
      • Contact: João Soares Felício, MD
  • Please Select
    • Sao Paulo, Please Select, Brazil
      • Not yet recruiting
      • Hospital 9 de Julho
      • Contact: Eduardo Lima, MD, PhD
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil
      • Not yet recruiting
      • Instituto Atena de Pesquisa Clinica LTDA
      • Contact: Maria Sanali Moura de Oliveira Paiva, MD
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Not yet recruiting
      • Hospital de Clínicas de Porto Alegre
      • Contact: Flávio Danni Fuchs, MD, PhD; Phone Number: (51) 3359-8000; Email: ffuchs@hcpa.edu.br
  • SE
    • Aracaju, SE, Brazil
      • Not yet recruiting
      • Centro de Pesquisa Clinica do Coracao
      • Contact: Fabio Silveira
      • Principal Investigator: Fabio Silveira, MD
  • SP
    • Bragança Paulista, SP, Brazil
      • Recruiting
      • Hospital Universitário São Francisco de Assis
      • Contact: Murillo Antunes
      • Principal Investigator: Murillo Antunes, MD
    • Campinas, SP, Brazil
      • Not yet recruiting
      • Instituto de Pesquisa Clínica de Campinas
      • Contact: Jose Francisco Saraiva
      • Principal Investigator: Jose Francisco Saraiva, MD
    • São Paulo, SP, Brazil
      • Not yet recruiting
      • Hospital M'Boi Mirim
      • Contact: Niklas Campos, MD
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil
      • Not yet recruiting
      • CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
      • Contact: Conrado Hoffmann Filho, MD, PhD; Email: conrado@corsanus.com.br
  • São Paulo
    • Campinas, São Paulo, Brazil
      • Not yet recruiting
      • LOEMA - Instituto de Pesquisa Clinica & Consultores LTDA.
      • Principal Investigator: Maria Helena Vidotti, MD
      • Contact: Maria Helena Vidotti
    • Indaiatuba, São Paulo, Brazil
      • Not yet recruiting
      • Indacor Serviços Médicos
      • Contact: Flávio Souza Brito, MD
    • São José Dos Campos, São Paulo, Brazil
      • Not yet recruiting
      • CIPES Centro Internacional de Pesquisa Clínica LTDA
      • Contact: Fabiana Goulart Marcondes Braga, MD, PhD
    • Votuporanga, São Paulo, Brazil
      • Not yet recruiting
      • Clínica Cardiológica
      • Contact: Elizabeth Espirito Santo Cestario, MD
    • Votuporanga, São Paulo, Brazil
      • Not yet recruiting
      • Santa Casa de Misericórdia de Votuporanga
      • Contact: Mauro E Hernandes, MD
      • Principal Investigator: Mauro E Hernandes, MD

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;
• 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, 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 (Estimated): December 31, 2023
• Study Completion (Estimated): July 1, 2024

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): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No