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Combination of Telmisartan 80 mg Plus Hydrochlorothiazide 12.5 mg to Telmisartan 80 mg in Patients Failed in Telmisartan 80 mg

Phase 3
Completed
Conditions
Hypertension
Registration Number
NCT00146341
Lead Sponsor
Boehringer Ingelheim
Brief Summary

To demonstrate that a fixed dose combination of telmisartan 80 mg plus HCTZ 12.5 mg is superior to telmisartan 80 mg alone in patients, who fail to respond adequately to telmisartan 80 mg monotherapy, in lowering seated trough diastolic blood pressure after eight weeks of treatment.

Detailed Description

This is a multi-centre, prospective, randomized, double-blind, parallel-group study in approximately 244 patients with a history of mild-to-moderate hypertensive who have been shown not to respond to telmisartan monotherapy.

All patients will enter a one-week screening phase prior to starting the eight-week open-label T80 mg period. At the end of four weeks, only patients who fail to respond to T80 mg (DBP \>= 90 mm Hg) will continue the treatment with T80 mg for another four weeks. At the end of eight weeks, only patients who fail to respond to T80 mg (DBP \>= 90 mm Hg) will be randomized, double-blind, to receive either T80 mg alone or the fixed dose combination of T80 mg plus HCTZ 12.5 mg for eight weeks. Seated BP will be taken 24 hours post-dose at each visit. Labs, ECG, and physical examination will be done at screening, at baseline and at the final visit.

Study Hypothesis:

The primary objective of the study, showing that fixed dose combination is superior to telmisartan 80 mg alone will be tested using the hypotheses given below.

H0: u T80/H12.5 - uT80 = 0 mm Hg versus H1: uT80/H12.5 - uT80 not equal 0 mm Hg, where uT80/H12.5 anduT80 represent the average reduction from baseline (Visit 4) in trough seated DBP for the fixed dose combination and telmisartan 80 mg, respectively.

Testing of the null hypothesis will be performed using a two-sided test of significance at an a-level (type-I error rate) of 0.05.

Comparison(s):

The primary efficacy endpoint will be the change from baseline in seated DBP 24 hours post-dose at the last visit during the double-blind treatment phase. The pre-dose measurement on visit 4 will be viewed as the baseline measurement.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
345
Inclusion Criteria
  1. History of mild-to-moderate hypertension defined by a mean seated DBP >=95 and <= 109 mmHg before inclusion in the open-label phase
  2. Patients who fail to respond adequately to telmisartan monotherapy (mean seated DBP >= 90 mmHg)
  3. Participants between 18 and 80 years of age
  4. Ability to provide written informed consent
Exclusion Criteria
  1. Patients taking more than three anti-hypertensive medications at the screening visit.

  2. Pre-menopausal women (last menstruation 1 year prior to start of screening):

    • Who are not surgically sterile (hysterectomy, tubal ligation)
    • Who are NOT practicing acceptable means of birth control or who do NOT plan to continue using an acceptable method throughout the study (acceptable methods of birth control include IUD, oral, implantable or injectable contraceptives)
  3. Any woman:

    • Who has a positive urine pregnancy test at screening (Visit 1)
    • Who is nursing
  4. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

    • SGPT(ALT) or SGOT(AST) greater than two times the upper limit of normal
    • Serum creatinine > 3.0 mg/dL (or 265 mol/L) or creatinine clearance < 0.6 ml/sec
  5. Clinically relevant hypokalaemia or hyperkalaemia

  6. Uncorrected volume depletion

  7. Uncorrected sodium depletion

  8. Primary aldosteronism

  9. Hereditary fructose intolerance

  10. Biliary obstructive disorders, cholestasis or moderate to severe hepatic insufficiency

  11. Known or suspected secondary hypertension

  12. Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney; post-renal transplant patients, presence of only one functioning kidney

  13. Congestive heart failure (NYHA functional class CHF III-IV)

  14. Unstable angina within the past three months

  15. Stroke within the past six months

  16. Myocardial infarction or cardiac surgery within the past three months

  17. PTCA within the past three months

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
The primary efficacy variable is change from baseline in seated DBP at trough (24 hours post-dosing) after eight weeks of randomized treatment or at last trough observation during the double-blind phase (i.e. last trough observation carried forward).
Secondary Outcome Measures
NameTimeMethod
Change from baseline in seated SBP, standing DBP and SBP at trough after eight weeks of randomized treatment or at last trough observation during the double-blind phase. The percentage of patients responding to the treatment. Safety.

Trial Locations

Locations (9)

Ruijin Hospital, School of Medicine

🇨🇳

Shanghai, China

No. 1 Hosp Affiliated to Med College

🇨🇳

Zhejiang Province, China

Beijing Tiantan Hospital

🇨🇳

Beijing, China

254 PLA Hospital

🇨🇳

Tianjin, China

China-Japan Friendship Hospital

🇨🇳

Beijing, China

Shanghai Changhai Hospital

🇨🇳

Shanghai, China

Peking Union Medical College Hospital

🇨🇳

Beijing, China

No. 1 Hospital Affiliated Nanjing

🇨🇳

Nanjing, China

Second Hospital Affiliated to Tianjin Med University

🇨🇳

Tianjin, China

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