Hypertension
Conditions
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.
Interventions
DRUGcandesartan cilexetil + chlorthalidone + amlodipine
Antihypertensive drugs in a single tablet (association candesartan cilexetil 16mg + chlorthalidone 12.5mg + amlodipine 5mg)
DRUGExforge HCT® (valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)
Antihypertensive drugs in a single tablet (association valsartan 160mg + hydrochlorothiazide 12.5mg + amlodipine 5mg)
Sponsors
Libbs Farmacêutica LTDA
Hospital Israelita Albert Einstein
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The experimental/comparator drug has different characteristics. To allow blinding, the Double-Dummy method will be performed, where study sites will receive two drug presentations (active and placebo), thus preventing any violation of blinding.
Intervention model description
A multicenter, double-blind, phase III, parallel, controlled and randomized clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change in systolic blood pressure (SBP) | 12 weeks | The primary efficacy endpoint is the mean change in systolic blood pressure, measured at the site, 12 weeks after starting treatment, compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants with blood pressure (SBP <140 and DBP<90 mmHg) | 12 weeks | Proportion of participants who reach the target blood pressure (SBP \<140 and DBP\<90mmHg) 4, 8 and 12 weeks after starting treatment |
| Participants with SBP <120 mmHg | 12 weeks | Proportion of participants who reach the target blood pressure of SBP \<120 mmHg 4, 8 and 12 weeks after starting treatment |
| Participants with SBP <140 mmHg | 12 weeks | Proportion of participants who reach target systolic blood pressure (SBP \<140 mmHg) 4, 8 and 12 weeks after starting treatment |
| Mean change in diastolic blood pressure (DBP) | 12 weeks | Variation in diastolic blood pressure 4, 6 and 12 weeks after starting treatment |
| Participants with reduction greater than or equal to 20 mmHg in SBP | 12 weeks | 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 |
| Participants with reduction greater than or equal to 10 mmHg in DBP | 12 weeks | 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 |
| Participants with DBP<90 mmHg | 12 weeks | Proportion of participants who reach the target diastolic blood pressure (DBP\<90 mmHg) 4, 8 and 12 weeks after starting treatment |
Countries
Brazil
Outcome results
None listed