Clinical trial NCT00926289: Telmisartan 80mg Plus Hydrochlorothiazide 25mg First Line in Moderate or Severe Hypertension
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-06-23
Enrollment: 894
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion criteria:

1. Ability to provide written informed consent in accordance with Good Clinical Practice and local legislation;
2. Age 18 years or older;
3. Patients with grade 2 or grade 3 hypertension as defined SBP\>=160 mmHg and DBP\>=100 mmHg at randomization
4. Ability to stop any current antihypertensive therapy without unacceptable risk to the patient (Investigator's discretion)

Exclusion criteria:

1. 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.
2. Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 a.m.
3. Known or suspected secondary hypertension (e.g., renal artery stenosis orphaeochromocytoma)
4. Mean in-clinic seated cuff SBP\>= 200 mmHg and/or DBP \>=120 mmHg
5. 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.
6. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney
7. Clinically relevant hypokalemia or hyperkalemia (i.e., \<3.5 mmol/L or \>5.5 mmol/L, may be rechecked for suspected error in result)
8. Uncorrected sodium or volume depletion
9. Primary aldosteronism.
10. Hereditary fructose intolerance
11. Biliary obstructive disorders (e.g., cholestasis) or hepatic insufficiency
12. Congestive heart failure New York Heart Association functional class Congestive Heart Failure III-IV (Refer to Appendix 10.3)
13. 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)
14. Clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the Investigator
15. Hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve
16. Patients whose diabetes has not been stable and controlled for at least the past 3 months as defined by an Glycosylated Hemoglobin \>=10%
17. Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin-II receptor antagonists
18. History of drug or alcohol dependency within 6 months prior to signing the informed consent form
19. Concomitant administration of any medications known to affect blood pressure, except medications allowed by the protocol
20. Any investigational drug therapy within 1 month of signing the informed consent
21. Known hypersensitivity to any component of the trial drugs (telmisartan, hydrochlorothiazide, or placebo)
22. 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)
23. 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

Primary outcomes:
measure: Change From Baseline in Mean Seated Trough Cuff Systolic Blood Pressure (SBP) to Week 7
timeFrame: Baseline and Week 7
Secondary outcomes:
measure: Change From Baseline in Mean Seated Trough Cuff SBP to Week 5
timeFrame: Baseline and Week 5
measure: Change From Baseline in Mean Seated Trough Cuff SBP to Week 3
timeFrame: Baseline and Week 3
measure: Change From Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) to Week 7
timeFrame: Baseline and Week 7
measure: Number of Patients With SBP Control (SBP < 140 mmHg) at Week 7
timeFrame: Week 7 timepoint
measure: Number of Patients With SBP Control (SBP < 140 mmHg) at Week 5
timeFrame: Week 5 timepoint
measure: Number of Patients With SBP Control (SBP < 140 mmHg) at Week 3
timeFrame: Week 3 timepoint
measure: Number of Patients With DBP Control (DBP < 90 mmHg) at Week 7
timeFrame: Week 7 timepoint
measure: Number of Patients With DBP Control (DBP < 90 mmHg) at Week 5
timeFrame: Week 5 timepoint
measure: Number of Patients With DBP Control (DBP < 90 mmHg) at Week 3
timeFrame: Week 3 timepoint
measure: Number of Patients With Blood Pressure (BP) Control at Week 7
timeFrame: Week 7 timepoint
measure: Number of Patients With BP Control at Week 7
timeFrame: Week 7 timepoint
measure: Number of Patients With Systolic Blood Pressure (SBP) Response at Week 7
timeFrame: Week 7 timepoint
measure: Number of Participants With DBP Response at Week 7
timeFrame: Week 7 timepoint
measure: BP Categories at Week 7
timeFrame: Week 7 timepoint
Other outcomes:
Locations:
city: Athens
country: United States
facility: 502.550.01008 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mobile
country: United States
facility: 502.550.01019 Boehringer Ingelheim Investigational Site
state: Alabama
city: Lomita
country: United States
facility: 502.550.01015 Boehringer Ingelheim Investigational Site
state: California
city: Colorado Springs
country: United States
facility: 502.550.01003 Boehringer Ingelheim Investigational Site
state: Colorado
city: Fort Lauderdale
country: United States
facility: 502.550.01014 Boehringer Ingelheim Investigational Site
state: Florida
city: Louisville
country: United States
facility: 502.550.01002 Boehringer Ingelheim Investigational Site
state: Kentucky
city: New Iberia
country: United States
facility: 502.550.01011 Boehringer Ingelheim Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: 502.550.01009 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Olive Branch
country: United States
facility: 502.550.01018 Boehringer Ingelheim Investigational Site
state: Mississippi
city: St. Louis
country: United States
facility: 502.550.01006 Boehringer Ingelheim Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: 502.550.01016 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: 502.550.01007 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: 502.550.01005 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: 502.550.01001 Boehringer Ingelheim Investigational Site
state: Ohio
city: Houston
country: United States
facility: 502.550.01017 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 502.550.01020 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 502.550.01012 Boehringer Ingelheim Investigational Site
state: Texas
city: Arlington
country: United States
facility: 502.550.01004 Boehringer Ingelheim Investigational Site
state: Virginia
city: Sofia
country: Bulgaria
facility: 502.550.35901 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35902 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35903 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35904 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35905 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35908 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35909 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35910 Boehringer Ingelheim Investigational Site
city: Sofia
country: Bulgaria
facility: 502.550.35911 Boehringer Ingelheim Investigational Site
city: Stara Zagora
country: Bulgaria
facility: 502.550.35906 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 502.550.86004 Boehringer Ingelheim Investigational Site
city: Guangzhou, Guangdong Province
country: China
facility: 502.550.86003 Boehringer Ingelheim Investigational Site
city: QingDao
country: China
facility: 502.550.86008 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 502.550.86001 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 502.550.86002 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 502.550.86009 Boehringer Ingelheim Investigational Site
city: Tianjin
country: China
facility: 502.550.86007 Boehringer Ingelheim Investigational Site
city: Zhengzhou
country: China
facility: 502.550.86010 Boehringer Ingelheim Investigational Site
city: Aigrefeuille S/Maine
country: France
facility: 502.550.3302D Boehringer Ingelheim Investigational Site
city: Aix-en-Provence
country: France
facility: 502.550.3305I Boehringer Ingelheim Investigational Site
city: Aubagne
country: France
facility: 502.550.3305G Boehringer Ingelheim Investigational Site
city: Briollay
country: France
facility: 502.550.3301H Boehringer Ingelheim Investigational Site
city: Cholet
country: France
facility: 502.550.3301K Boehringer Ingelheim Investigational Site
city: Corsept
country: France
facility: 502.550.3302I Boehringer Ingelheim Investigational Site
city: Donges
country: France
facility: 502.550.3302C Boehringer Ingelheim Investigational Site
city: La Montagne
country: France
facility: 502.550.3302B Boehringer Ingelheim Investigational Site
city: Louvigné de Bais
country: France
facility: 502.550.3306A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3303A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3303D Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3303F Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3304A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3304D Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3304F Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3304J Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 502.550.3305A Boehringer Ingelheim Investigational Site
city: Murs Erigne
country: France
facility: 502.550.3301A Boehringer Ingelheim Investigational Site
city: Murs-Erigne
country: France
facility: 502.550.3301I Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: 502.550.3302A Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: 502.550.3302E Boehringer Ingelheim Investigational Site
city: Parcay-les-Pins
country: France
facility: 502.550.3301E Boehringer Ingelheim Investigational Site
city: Roquevaire
country: France
facility: 502.550.3303C Boehringer Ingelheim Investigational Site
city: Segre
country: France
facility: 502.550.3301F Boehringer Ingelheim Investigational Site
city: St Aubin les Châteaux
country: France
facility: 502.550.3302G Boehringer Ingelheim Investigational Site
city: St Jouan des Guerets
country: France
facility: 502.550.3306F Boehringer Ingelheim Investigational Site
city: Thouars
country: France
facility: 502.550.3307A Boehringer Ingelheim Investigational Site
city: Vihiers
country: France
facility: 502.550.3301J Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99501 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99502 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99503 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99504 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99505 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99506 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99507 Boehringer Ingelheim Investigational Site
city: Tbilisi
country: Georgia
facility: 502.550.99508 Boehringer Ingelheim Investigational Site
city: Cheonan
country: Korea, Republic of
facility: 502.550.82008 Boehringer Ingelheim Investigational Site
city: Daegu
country: Korea, Republic of
facility: 502.550.82009 Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: 502.550.82001 Boehringer Ingelheim Investigational Site
city: Gwangju
country: Korea, Republic of
facility: 502.550.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82005 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82006 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82007 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82011 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82012 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 502.550.82013 Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: 502.550.82004 Boehringer Ingelheim Investigational Site
city: Wonju
country: Korea, Republic of
facility: 502.550.82010 Boehringer Ingelheim Investigational Site
city: Baia Mare Maramures
country: Romania
facility: 502.550.40002 Boehringer Ingelheim Investigational Site
city: Braila
country: Romania
facility: 502.550.40003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 502.550.40001 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 502.550.40010 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 502.550.40012 Boehringer Ingelheim Investigational Site
city: Cluj Napoca
country: Romania
facility: 502.550.40009 Boehringer Ingelheim Investigational Site
city: Cluj Napoca
country: Romania
facility: 502.550.40011 Boehringer Ingelheim Investigational Site
city: Iasi
country: Romania
facility: 502.550.40006 Boehringer Ingelheim Investigational Site
city: Oradea
country: Romania
facility: 502.550.40004 Boehringer Ingelheim Investigational Site
city: Sibiu
country: Romania
facility: 502.550.40005 Boehringer Ingelheim Investigational Site
city: Tg. Mures
country: Romania
facility: 502.550.40008 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07005 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 502.550.07006 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 502.550.07007 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 502.550.07008 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 502.550.07009 Boehringer Ingelheim Investigational Site
city: St.Petersburg
country: Russian Federation
facility: 502.550.07010 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Zhu DL, Bays H, Gao P, Mattheus M, Voelker B, Ruilope LM. Efficacy and tolerability of initial therapy with single-pill combination telmisartan/hydrochlorothiazide 80/25 mg in patients with grade 2 or 3 hypertension: a multinational, randomized, double-blind, active-controlled trial. Clin Ther. 2012 Jul;34(7):1613-24. doi: 10.1016/j.clinthera.2012.05.007. Epub 2012 Jun 19.