Efficacy and Safety Study of the Fixed-dose Combination of Olmesartan + Indapamide When Compared to the Isolated Drugs in the Treatment of Hypertension.

Study Overview
=================
Brief Summary
-----------------
Phase III clinical trial, multicenter of non-inferiority, randomized, single-blind evaluation of fixed-dose combination of olmesartan + indapamide compared to the isolated drugs in the treatment of hypertension.

Detailed Description
-----------------
This study is designed for the treatment of essential hypertension. It is performed in participants of both sexes, over 18 years of age, who have essential hypertension with diastolic blood pressure between 90 mmHg and 110 mmHg. The rationale for studying the fixed dose combination is the possibility to enhance compliance and simplify treatment.

Official Title
-----------------
Randomized, Single-Blind, Multicenter, Phase III, Non-Inferiority Clinical Trial to Evaluate the Efficacy and Safety of the Fixed-dose Combination of Olmesartan + Indapamide When Compared to the Isolated Drugs in the Treatment of Hypertension.

Conditions
-----------------
Hypertension, Hypertension,Essential

Intervention / Treatment
-----------------
* Drug: fixed-dose of olmesartan 20mg/40 mg + indapamide 1,5 mg
* Drug: Isolated drugs Olmesartan (20 mg or 40 mg) and Indapamide (1,5 mg)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have signed the informed consent form; Participants of both genders aged ≥ 18 years; Essential hypertension based on a Diastolic Blood Pressure (DBP) > 90 mmHg and < 110 mmHg; Patients with no treatment or on antihypertensive therapy taking up to two anti-hypertensives; Possibility of discontinuing previous antihypertensive medication during the washout period. Exclusion Criteria: Essential hypertension based on a Diastolic Blood Pressure (DBP) ≥ 110mmHg and Systolic Blood Pressure (SBP) ≥ 180 mmHg; Secondary hypertension; Participants with Body Mass Index (BMI) > 35 Kg/m2; Non-controlled types 1 and 2 diabetes mellitus (HbA1 > 8,5%); Myocardial infarction, coronary surgery or coronary angioplasty with or without stent placement, in the last 6 months; Unstable angina; Participants with coronary heart disease taking beta-blockers; Clinically manifest heart failure; History of cardiac arrhythmia; Moderate and severe heart valve disease; Stroke or transient ischemic attack in the last 6 months; Chronic disease of any nature that contraindicates the participant's participation according to the investigator's judgment, in particular renal failure with glomerular filtration rate < 45 ml/min, serum potassium levels ≥ 5,5 mEq/L or ≤ 3,5 mEq/L, hepatopathies, or SGOT, SGPT or bilirubin levels 3 times above the normal upper limit, and blood dyscrasias; Known allergies or contraindication to the use of the study medication components; Female participants who are pregnant, breastfeeding or who want to become pregnant; COVID-19 symptoms; Post COVID-19 syndrome with cardiovascular impairment; Subjects who have participated in other study within the 12 months prior to screening (unless benefit is justified by the researcher).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed-dose Olmesartan 20mg/40 mg + Indapamide 1,5 mg<br> | Drug: fixed-dose of olmesartan 20mg/40 mg + indapamide 1,5 mg<br>* Fixed-dose of Olmesartan 20mg or 40 mg + Indapamide 1,5 mg oral administration, once a day for 12 weeks. Initially, the participant will be treated with Olmesartan 20mg + Indapamide 1,5 mg. If after 6 weeks the diastolic blood pressure is above 90 mmHg, the dose will be changed to fixed dose of Olmesartan 40 mg + Indapamide 1,5 mg.<br>|
| Active Comparator: Isolated drugs Olmesartan (20 mg or 40 mg) and Indapamide (1,5 mg)<br> | Drug: Isolated drugs Olmesartan (20 mg or 40 mg) and Indapamide (1,5 mg)<br>* Isolated drugs Olmesartan (20 mg or 40 mg) and Indapamide (1,5 mg) oral administration, once a day for 12 weeks. Initially, the participant will be treated with Benicar® (olmesartan) 20mg and Natrilix® (indapamide) 1,5 mg. If after 6 weeks the diastolic blood pressure is above 90 mmHg, the dose of Benicar® (olmesartan) will be changed to 40 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-inferiority of fixed dose association of olmesartan + indapamide compared to the isolated drugs in the treatment of hypertension. | To evaluate the non-inferiority of the fixed dose association of olmesartan + indapamide to the isolated drugs in the change of the diastolic blood pressure from baseline to 12 week endpoint through Ambulatory Blood Pressure Monitoring. | 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic Blood Pressure Control | Proportion of participants achieving a diastolic blood pressure below 90 mmHg | 12 weeks of treatment | 
| Systolic Blood Pressure Control | Proportion of participants achieving a systolic blood pressure below 140 mmHg | 12 weeks of treatment | 
| Proportion of systolic and diastolic treatment response | Proportion of participants achieving a systolic blood pressure reduction greater than 20 mmHg and a diastolic blood pressure reduction greater than 10 mmHg. | 12 weeks of treatment | 
| Systolic and diastolic blood pressure variation by ABPM exam | Systolic and diastolic blood pressure variation by ABPM examination from the baseline period compared to the result after 12 weeks of treatment; | 12 weeks of treatment | 
| Patients responses to the treatment satisfaction questionnaire | Patients responses to a questionnaire regarding if they are satisfied with the treatment. | 12 weeks of treatment | 
| Tolerability and occurrence of adverse events (AEs) during the study period. | Tolerability and occurrence of adverse events (AEs) during the study period in both study arms. | 12 weeks of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
olmesartan, olmesartan medoxomil, indapamide, hypertension