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

Hypertension Clinical Trial

— OPTION TREAT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05920005
• Other study ID #: LB2009
• Status: Recruiting
• Phase: Phase 3
• Start date: August 22, 2023
• Est. completion date: July 1, 2024

Study information

• Verified date: June 2023
• Source: Hospital Israelita Albert Einstein
• Contact: Vagner Madrini Junior, MD
• Phone: +55 11 2151-5915
• Email: vagner.junior[@]einstein.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 698
• Est. completion date: July 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• candesartan cilexetil + chlorthalidone + amlodipine
Antihypertensive drugs in a single tablet (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg)
• Exforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)
Antihypertensive drugs in a single tablet (association valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)

Locations

Country	Name	City	State
Brazil	Centro de Pesquisa Clínica do Coração	Aracaju	SE
Brazil	Hospital Universita´rio Joao de Barros Barreto - UFPA	Belém	Pará
Brazil	Hospital Universitário São Francisco de Assis	Bragança Paulista	SP
Brazil	Instituto de Pesquisa Clínica de Campinas	Campinas	SP
Brazil	LOEMA - Instituto de Pesquisa Clinica & Consultores LTDA.	Campinas	São Paulo
Brazil	Centro de Pesquisas em Diabetes e Doenc¸as Endo´crino Metabo´licas LTDA	Fortaleza	Ceará
Brazil	Indacor Servic¸os Me´dicos	Indaiatuba	São Paulo
Brazil	CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda	Joinville	Santa Catarina
Brazil	Centro de Pesquisas Clinicas Dr. Marco Mota (Centro Universitario Cesmac/ Hospital do Coração de Alagoas)	Maceió	Alagoas
Brazil	Instituto Atena de Pesquisa Clinica LTDA	Natal	Rio Grande Do Norte
Brazil	Santa Casa de Misericórdia de Passos	Passos	MG
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Urgência e Emergência de Rio Branco	Rio Branco	AC
Brazil	Hospital Universita´rio Pedro Ernesto/UERJ	Rio De Janeiro
Brazil	CIPES Centro Internacional de Pesquisa Cli´nica LTDA	São José Dos Campos	São Paulo
Brazil	Hospital 9 de Julho	Sao Paulo	Please Select
Brazil	Associac¸a~o Lar Sa~o Francisco de Assis na Provide^ncia de Deus	São Paulo
Brazil	Hospital M'Boi Mirim	São Paulo	SP
Brazil	InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP	São Paulo
Brazil	Vitoria Clinical Research Institute LTDA	Vitória	Espírito Santo
Brazil	Clínica Cardiológica	Votuporanga	São Paulo
Brazil	Santa Casa de Misericordia de Votuporanga	Votuporanga	São Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein	Libbs Farmacêutica LTDA

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean change in diastolic blood pressure (DBP)	Variation in diastolic blood pressure 4, 6 and 12 weeks after starting treatment	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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