Telmisartan 80mg Plus Hydrochlorothiazide 25mg First Line in Moderate or Severe Hypertension

Study Overview
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Brief Summary
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The primary objective of this trial is to demonstrate that the fixed-dose combination of T80/HCTZ25 is superior as first line therapy in reducing seated trough cuff Systolic Blood Pressure(SBP) compared to the monotherapy of T80 in patients with grade 2 or grade 3 hypertension (SBP>=160 mmHg and Diastolic Blood Pressure(DBP)>=100 mmHg).

Official Title
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A Randomised, Double-blind, Double Dummy, Active Controlled, Parallel Group, Forced Titration Study to Compare the Fixed-dose Combination of Telmisartan 80mg Plus Hydrochlorothiazide 25mg (T80/HCTZ25) Versus Telmisartan 80mg (T80) Monotherapy as First Line Therapy in Patients With Grade 2 or Grade 3 Hypertension (Systolic Blood Pressure (SBP) >=160 mmHg and Diastolic Blood Pressure (DBP) >=100 mmHg)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Telmisartan
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Ability to provide written informed consent in accordance with Good Clinical Practice and local legislation; Age 18 years or older; Patients with grade 2 or grade 3 hypertension as defined SBP>=160 mmHg and DBP>=100 mmHg at randomization Ability to stop any current antihypertensive therapy without unacceptable risk to the patient (Investigator's discretion) Exclusion criteria: Pre-menopausal women (last menstruation <=1 year prior to signing informed consent) who: a) are not surgically sterile; or b) are nursing, or c) are pregnant, or d) are of childbearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the trial. The only acceptable methods of birth control are: Intra-Uterine Device (IUD), Oral contraceptives, Implantable or injectable contraceptives, Estrogen patch Hormonal birth control should have been in use for at least three months before the study and continue at least until the next menstrual period after completing the study. Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m. Known or suspected secondary hypertension (e.g., renal artery stenosis orphaeochromocytoma) Mean in-clinic seated cuff SBP>= 200 mmHg and/or DBP >=120 mmHg Renal dysfunction as defined by the following laboratory parameters: Serum creatinine >3.0 mg/dL (or >265 umol/L) and/or known creatinine clearance of <30 ml/min and/or clinical markers of severe renal impairment. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney Clinically relevant hypokalemia or hyperkalemia (i.e., <3.5 mmol/L or >5.5 mmol/L, may be rechecked for suspected error in result) Uncorrected sodium or volume depletion Primary aldosteronism. Hereditary fructose intolerance Biliary obstructive disorders (e.g., cholestasis) or hepatic insufficiency Congestive heart failure New York Heart Association functional class Congestive Heart Failure III-IV (Refer to Appendix 10.3) Contra-indication to a placebo run-in period (e.g., stroke with-in the past 6 months, myocardial infarction, cardiac surgery, percutaneous transluminal coronary angioplasty, unstable angina or coronary artery bypass graft within the past 3 months prior to start of run in period) Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve Patients whose diabetes has not been stable and controlled for at least the past 3 months as defined by an Glycosylated Hemoglobin >=10% Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin-II receptor antagonists History of drug or alcohol dependency within 6 months prior to signing the informed consent form Concomitant administration of any medications known to affect blood pressure, except medications allowed by the protocol Any investigational drug therapy within 1 month of signing the informed consent Known hypersensitivity to any component of the trial drugs (telmisartan, hydrochlorothiazide, or placebo) History of non-compliance or inability to comply with prescribed medications or protocol procedures (less than 80% or more than 120%, especially during run-in) Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of the trial medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Telmisartan<br>Telmisartan 80 mg | Drug: Telmisartan<br>* Telmisartan 80mg<br>|
| Experimental: Telmisartan/hydrochlorothiazide<br>Telmisartan80mg/Hydrochlorothiazide25mg | Drug: Telmisartan<br>* Telmisartan 80mg<br>Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide25mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Trough Cuff Systolic Blood Pressure (SBP) to Week 7 | The SBP value at baseline was subtracted from the SBP value at Week 7. | Baseline and Week 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Trough Cuff SBP to Week 5 | The SBP value at baseline was subtracted from the SBP value at Week 5. | Baseline and Week 5 | 
| Change From Baseline in Mean Seated Trough Cuff SBP to Week 3 | The SBP value at baseline was subtracted from the SBP value at Week 3. | Baseline and Week 3 | 
| Change From Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) to Week 7 | The DBP value at baseline was subtracted from the DBP value at Week 7. | Baseline and Week 7 | 
| Number of Patients With SBP Control (SBP < 140 mmHg) at Week 7 | SBP control is defined as SBP < 140 mmHg. | Week 7 timepoint | 
| Number of Patients With SBP Control (SBP < 140 mmHg) at Week 5 | SBP control is defined as SBP < 140 mmHg | Week 5 timepoint | 
| Number of Patients With SBP Control (SBP < 140 mmHg) at Week 3 | SBP control is defined as SBP < 140 mmHg | Week 3 timepoint | 
| Number of Patients With DBP Control (DBP < 90 mmHg) at Week 7 | DBP control is defined as DBP<90 mmHg | Week 7 timepoint | 
| Number of Patients With DBP Control (DBP < 90 mmHg) at Week 5 | DBP control is defined as DBP<90 mmHg | Week 5 timepoint | 
| Number of Patients With DBP Control (DBP < 90 mmHg) at Week 3 | DBP control is defined as DBP<90 mmHg | Week 3 timepoint | 
| Number of Patients With Blood Pressure (BP) Control at Week 7 | BP control is defined as SBP<140 mmHg and DBP < 90 mmHg and is adjusted for baseline SBP | Week 7 timepoint | 
| Number of Patients With BP Control at Week 7 | BP control is defined as SBP<140 mmHg and DBP < 90 mmHg and is adjusted for baseline DBP | Week 7 timepoint | 
| Number of Patients With Systolic Blood Pressure (SBP) Response at Week 7 | SBP response is defined as SBP<140 mmHg or a reduction of >= 15 mmHg | Week 7 timepoint | 
| Number of Participants With DBP Response at Week 7 | DBP response is defined as DBP<90 mmHg or a reduction of >= 10 mmHg | Week 7 timepoint | 
| BP Categories at Week 7 | BP categories comprise: BP optimal (SBP <120 mmHg and DBP <80 mmHg) BP normal (SBP <130 mmHg and DBP <85 mmHg but not 'optimal') BP high normal (SBP <140 mmHg and DBP <90 mmHg but not 'normal') Grade 1 hypertension (SBP <160 mmHg and DBP <100 mmHg but not 'high normal') Grade 2 hypertension (SBP <180 mmHg and DBP <110 mmHg but not 'Grade 1 hypertension') Grade 3 hypertension (SBP ≥180 mmHg or DBP ≥110 mmHg) | Week 7 timepoint |