Clinical trial NCT00239369: Telmisartan80/HCTZ25 Versus Telmisartan80/HCTZ12.5 in Hypertension Not Responding to Telmisartan80/HCTZ12.5
Official title: A Prospective Randomised Study to Compare a Fixed Dose Combination of Telmisartan 80 mg Plus Hydrochlorothiazide 25 mg With a Fixed Dose Combination of Telmisartan 80 mg Plus Hydrochlorothiazide 12.5 mg in Patients With Uncontrolled Hypertension Who Fail to Respond Adequately to Treatment With a Fixed Dose Combination of Telmisartan 80 mg Plus Hydrochlorothiazide 12.5 mg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-10-17
Enrollment: 713
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 a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide 25 mg (T80/H25) is superior in reducing blood pressure after eight weeks compared with a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide 12.5 mg (T80/H12.5) in patients who fail to respond to six weeks treatment with T80/H12.5.

Detailed description: Adult patients with high blood pressure who are currently taking one, two or three blood pressure treatments will be asked to take part in the study. It is expected that about 1,600 patients in seventeen countries will enter the screening part of the study and approximately 480 of these patients will be allocated to double-blind randomised study treatment. The study will last for approximately fifteen weeks. Patients will visit the study doctor five times for assessment. After informed consent, patients will start a screening period for four to ten days. During the screening period, patients must take their usual blood pressure treatment but will stop this by the date of the next visit. If the patient is suitable for this study, they will then start run-in treatment period with telmisartan 80 mg plus hydrochlorothiazide 12.5 mg (T80/H12.5) taken as a single tablet once per day for approximately six weeks.

At the end of the run-in treatment period, if the diastolic blood pressure (DBP) is below 90 mmHg, the patient will not proceed as their blood pressure is already controlled by T80/H12.5. If the DBP is 90 mmHg or greater they will start the randomised study treatment period and be randomly allocated to double-blind treatment with either telmisartan 80 mg plus hydrochlorothiazide 25 mg(T80/H25) or T80/H12.5 taken as a single tablet once per day for eight weeks. They will also receive a placebo tablet (a dummy tablet which contains no active ingredient) every day.

They will visit the clinic four weeks and eight weeks later for assessment of their blood pressure and general health. Their participation in the study is complete eight weeks after the start of the randomised treatment period.

Study Hypothesis:

The trial hypothesis is that the reduction in seated trough DBP (i.e., seated trough DBP at the end of the randomised treatment period compared with the seated trough DBP at the start of the randomised treatment period) will be greater in the T80/H25 group compared with the T80/H12.5 group.

Comparison(s):

The efficacy and safety of the two trial treatments (T80/H25 versus T80/H12.5) will be compared. Trough blood pressure is the blood pressure 24 hours after the last dose of trial medication.

Eligibility criteria: Inclusion criteria:

* Essential hypertension.
* Currently taking between one and three antihypertensive medications at a stable dose for at least four weeks before Visit 1.
* Blood pressure not adequately controlled on existing treatment before entry (inadequate control defined as seated DBP \>= 95 mmHg on one current antihypertensive medication or DBP \>= 90 mmHg on two or more current antihypertensive medication(s).
* Failure to respond to six weeks treatment with T80/H12.5. (Failure to respond defined as seated DBP \>= 90 mmHg at six weeks. This criterion will be assessed at Visit 3.)
* Willing and able to provide written informed consent.

Exclusion criteria:

* Women of child-bearing potential NOT practising acceptable means of birth control, positive serum pregnancy test, breastfeeding.
* Known or suspected secondary hypertension.
* Mean SBP \>= 200 mmHg.
* Severe hepatic or renal impairment.
* Bilateral renal artery stenosis (or in a solitary kidney), post-renal transplant or only one functioning kidney.
* Clinically relevant hypokalaemia or hyperkalaemia.
* Uncorrected volume or sodium depletion, primary aldosteronism.
* Hereditary fructose intolerance.
* Previous symptoms of angioedema after ACE inhibitors or angiotensin-II receptor antagonists.
* Drug or alcohol dependency within the previous six months.
* Administration of any medication known to affect blood pressure.
* Concurrent participation in another clinical trial or any investigational therapy.
* Hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve.
* Allergic hypersensitivity to any component of the formulations under investigation.
* Concomitant therapy with lithium, cholestyramine or colestipol resins. non-compliance with study medication (less than 80% or more than 120%) during th e run-in treatment period.
* Any other clinical condition which, in the opinion of the investigator, would not allow safe administration of telmisartan or hydrochlorothiazide.

Primary outcomes:
measure: Change from baseline in trough seated DBP
timeFrame: 8 weeks
Secondary outcomes:
measure: Change from baseline in trough seated SBP
timeFrame: 8 weeks
measure: Change from baseline in trough standing DBP and SBP
timeFrame: 8 weeks
measure: The proportion of patients achieving DBP control (trough seated DBP<90 mmHg).
timeFrame: 8 weeks
measure: The proportion of patients achieving DBP response (trough seated DBP<90 mmHg or trough seated DBP reduction from baseline ≥10 mmHg).
timeFrame: 8 weeks
measure: The proportion of patients achieving SBP response (trough seated SBP<140 mmHg or trough seated SBP reduction from baseline ≥10 mmHg).
timeFrame: 8 weeks
measure: The proportion of patients achieving SBP response (trough seated SBP<140 mmHg or trough seated SBP reduction from baseline ≥20 mmHg)
timeFrame: 8 weeks
measure: The proportion of patients in trough seated BP categories: opt.: SBP<120 mmHg and DBP<80 mmHg., norm.: SBP<130 mmHg and DBP<85 mmHg and not optimal, high-normal: SBP<140 mmHg and DBP<90 mmHg and not optimal or normal, high: SBP ≥140 mmHg or DBP ≥90 mmHg
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Birker?d
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Haderslev
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Odder
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: R?dovre
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Vildbjerg
country: Denmark
facility: Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Joensuu
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Kokkola
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Angers
country: France
facility: ALTI
city: Angers
country: France
facility: ALTI
city: Bobigny
country: France
facility: Hopital Avicenne
city: Paris
country: France
facility: Mg Recherches
city: Ellefeld
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Florsheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Haag
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Ingelheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Nurnberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rodgau-Dudenhofen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Unterschneidheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: Boehringer Ingelheim Investigational Site
city: Birr
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Carrigallen
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Dublin 18
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Dublin 24
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Dublin 9
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Enniscorthy,
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Gorey
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Mallow
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: New Ross
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Toomevara
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Broni (PV)
country: Italy
facility: Ospedale Arnaboldi
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universita di Ferrara
city: Roma
country: Italy
facility: IRCCS San Raffaele
city: Vittorio Veneto (TV)
country: Italy
facility: Ospedale Civile
city: Incheon
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Kuching, Sarawak
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Bennebroek
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Ewijk
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Helmond
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Hoogwoud
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Nijverdal
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Rijswijk
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Roelofarendsveen
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Rotterdam
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Elverum
country: Norway
facility: Boehringer Ingelheim Investigational Site
city: Moelv
country: Norway
facility: Boehringer Ingelheim Investigational Site
city: Oslo
country: Norway
facility: Boehringer Ingelheim Investigational Site
city: Skedsmokorset
country: Norway
facility: Boehringer Ingelheim Investigational Site
city: Tolvsr?d
country: Norway
facility: Boehringer Ingelheim Investigational Site
city: Bellville
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Durban
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Johannesburg
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Johannesburg
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Lenasia South
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Lenasia
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Midrand
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Pretoria
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Badalona / Barcelona
country: Spain
facility: Hospital Municipal de Badalona
city: Galdakao / Vizcaya
country: Spain
facility: Hospital de Galdakao
city: Jerez De La Frontera / Cadiz
country: Spain
facility: Hospital Gral. Jerez de la Frontera
city: L'Hospitalet De Llobregat / Barcelona
country: Spain
facility: C.A.P. Mosen Cinto Verdaguer
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Mara?on
city: Mataro (Barcelona)
country: Spain
facility: C.A.P. Ronda Cerdanya
city: Mostoles / Madrid
country: Spain
facility: Hospital General de Mostoles - Medicina Interna
city: Santiago de Compostela
country: Spain
facility: Hospital del Conxo
city: Eksjo
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Karlstad
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Karlstad
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Uddevalla
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: Bellinzona
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: St. Imier
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: Vezia
country: Switzerland
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: BIL UK / Ireland
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: