Clinical trial NCT05920005: Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension
Official title: A Multicenter, Double-blind, Controlled, Randomized Trial to Evaluate the Association Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT®️ for Systemic Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: Libbs Farmacêutica LTDA
First posted: 2023-06-27
Enrollment: 698
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicenter, double-blind, phase III, parallel, controlled and randomized clinical trial.
Primary purpose: TREATMENT

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.

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;
* 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;

Primary outcomes:
measure: Mean change in systolic blood pressure (SBP)
timeFrame: 12 weeks
Secondary outcomes:
measure: Mean change in diastolic blood pressure (DBP)
timeFrame: 12 weeks
measure: Participants with blood pressure (SBP <140 and DBP<90 mmHg)
timeFrame: 12 weeks
measure: Participants with SBP <120 mmHg
timeFrame: 12 weeks
measure: Participants with SBP <140 mmHg
timeFrame: 12 weeks
measure: Participants with DBP<90 mmHg
timeFrame: 12 weeks
measure: Participants with reduction greater than or equal to 20 mmHg in SBP
timeFrame: 12 weeks
measure: Participants with reduction greater than or equal to 10 mmHg in DBP
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Rio Branco
country: Brazil
facility: Hospital de Urgência e Emergência de Rio Branco
state: AC
city: Maceió
country: Brazil
facility: Centro de Pesquisas Clinicas Dr. Marco Mota (Centro Universitario Cesmac/ Hospital do Coração de Alagoas)
state: Alagoas
city: Fortaleza
country: Brazil
facility: Centro de Pesquisas em Diabetes e Doenças Endócrino Metabólicas LTDA
state: Ceará
city: Vitória
country: Brazil
facility: Vitoria Clinical Research Institute LTDA
state: Espírito Santo
city: Passos
country: Brazil
facility: Santa Casa de Misericórdia de Passos
state: MG
city: Belém
country: Brazil
facility: Hospital Universitário Joao de Barros Barreto - UFPA
state: Pará
city: Sao Paulo
country: Brazil
facility: Hospital 9 de Julho
state: Please Select
city: Natal
country: Brazil
facility: Instituto Atena de Pesquisa Clinica LTDA
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: CMEP Centro Multidisciplinar de Ensino Especializado e Pesquisa Ltda
state: Santa Catarina
city: Aracaju
country: Brazil
facility: Centro de Pesquisa Clínica do Coração
state: SE
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário São Francisco de Assis
state: SP
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clínica de Campinas
state: SP
city: São Paulo
country: Brazil
facility: Hospital M'Boi Mirim
state: SP
city: Campinas
country: Brazil
facility: LOEMA - Instituto de Pesquisa Clinica & Consultores LTDA.
state: São Paulo
city: Indaiatuba
country: Brazil
facility: Indacor Serviços Médicos
state: São Paulo
city: São José Dos Campos
country: Brazil
facility: CIPES Centro Internacional de Pesquisa Clínica LTDA
state: São Paulo
city: Votuporanga
country: Brazil
facility: Clínica Cardiológica
state: São Paulo
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericordia de Votuporanga
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Hospital Universitário Pedro Ernesto/UERJ
city: São Paulo
country: Brazil
facility: InCor - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP
city: São Paulo
country: Brazil
facility: Associação Lar São Francisco de Assis na Providência de Deus
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Patrícia Oliveira Guimarães, MD, PhD
role: STUDY_DIRECTOR
References: