Clinical trial NCT00267943: Open-label Follow-up Trial of Fixed Dose Combination of Telmisartan + Hydrochlorothiazide in Hypertensive Patients
Official title: An Open-label Follow-up Trial of the Efficacy and Safety of Chronic Administration of the Fixed Dose Combination of Telmisartan 80 mg + Hydrochlorothiazide 25 mg Tablets Alone or in Combination With Other Antihypertensive Medications in Patients With Hypertension.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-12-22
Enrollment: 639
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective is to assess the efficacy and safety of the fixed dose combination of telmisartan 80 mg + hydrochlorothiazide 25 mg (T80/H25) alone or in addition to other antihypertensive therapies during open-label, long-term treatment.

Detailed description: Patients with a history of hypertension who completed a preceding trial (number 502.480) within the previous fourteen (14) days will be considered for entry to this long-term open-label trial. All patients will receive 'T80/H25'. Additional antihypertensive therapy will be allowed if the patients' blood pressure is not well controlled. \[In the preceding double-blind trial 502.480, patients who failed to respond to the fixed dose combination of telmisartan 80 mg '+' hydrochlorothiazide 12.5 mg (T80/H12.5) were randomised to 'T80/H12.5' or T80H25 for eight weeks.\] This is a multi-centre, multinational trial with approximately 80 study centres participating. Only study centres participating in the preceding trial 502.480 can enter patients into this open-label trial. It is anticipated that a maximum of 480 patients will be entered into the trial in seventeen countries. Each trial centre is expected to enter between four and twenty-four patients.

Enrollment of patients into this trial will finish when the last patient completes the preceding trial 502.480. At this time, centres will be notified of the termination of recruitment and will not be authorized to include any further patients.

Patients will visit the clinic one month, three months and six months later for assessment of their blood pressure and general health. Their participation in the study is complete six months after the start of the treatment period.

Study Hypothesis:

No statistical hypothesis will be tested. Descriptive statistics will be used to characterise the effects of treatment with T80/H25 with and without other antihypertensive treatments.

Comparison(s):

The proportion of patients achieving DBP control will be summarised by the total number of patients in the trial as well as by the maximum achieved dose level according to the two categories of T80/H25 alone (T80/H25) and with other antihypertensive medication added (T80/H25/other). An additional sub-group summary by the treatment group in the preceding trial 502.480 (T80/H12.5 and T80/H25) will also be presented.

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 of preceding trial 502.480.
* Blood pressure not adequately controlled on existing treatment before entry to preceding trial 502.480 (inadequate control defined as seated DBP \>= 95 mmHg on one current antihypertensive medication or DBP \>= 90 mmHg on two or more current antihypertensive medications).
* Failure to respond to six weeks run-in treatment with T80/H12.5 in preceding trial 502.480. (Failure to respond defined as seated DBP \>= 90 mmHg.)
* 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.
* Clinically significant change in ECG reported as adverse event in preceding trial 502.480.
* Any medical condition developing in preceding trial 502.480 that could be worsened by telmisartan/HCTZ (80/25).
* Discontinuation from preceding 502.480 trial for adverse event or any other reason.
* 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 six months prior to entry to 502.480. 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 the preceding 502.480 trial.
* Any other clinical condition which, in the opinion of the investigator, would not allow safe administration of telmisartan or hydrochlorothiazide.

Primary outcomes:
measure: Proportion of patients achieving diastolic blood pressure (DBP) control 24 hours after last dose
timeFrame: at 6 months
Secondary outcomes:
measure: Change from baseline in trough seated DBP.
timeFrame: at 6 months
measure: Change from baseline in trough seated systolic blood pressure (SBP)
timeFrame: at 6 months
measure: Proportion of patients achieving DBP response (trough seated DBP<90 mmHg or trough seated DBP reduction from baseline ≥10 mmHg)
timeFrame: at 6 months
measure: Proportion of patients achieving SBP response (trough seated SBP<140 mmHg or trough seated SBP reduction from baseline ≥10 mmHg)
timeFrame: at 6 months
measure: Proportion of patients achieving SBP response (trough seated SBP<140 mmHg or trough seated SBP reduction from baseline ≥20 mmHg)
timeFrame: at 6 months
measure: Proportion of patients in the trough seated BP category optimal
timeFrame: at 6 months
measure: Proportion of patients in the trough seated BP category normal
timeFrame: at 6 months
measure: Proportion of patients in the trough seated BP category high-normal
timeFrame: at 6 months
measure: Proportion of patients in the trough seated BP category high
timeFrame: at 6 months
measure: Proportion of patients requiring additional antihypertensive therapy to achieve DBP control
timeFrame: at 6 months
measure: Additional reduction in BP by the use of additional antihypertensive therapy
timeFrame: at 6 months
measure: Time to starting additional antihypertensive therapy
timeFrame: within 6 months
measure: Incidence and intensity of Adverse events
timeFrame: 6 month
measure: Physical examinations
timeFrame: 6 month
measure: Change in laboratory parameters
timeFrame: 6 month
measure: 12-Lead Electrocardiogramm ECG
timeFrame: 6 month
measure: Vital Signs (pulse rate, SBP, DBP)
timeFrame: 6 month
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: Turku
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Turku
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Angers
country: France
facility: ALTI
city: Bobigny
country: France
facility: Hopital Avicenne
city: Paris
country: France
facility: Mg Recherches
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: 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: Templeshannon
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: Beerzeveld
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Bennebroek
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Ewijk
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: Bellville
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Durban
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: Newtown
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Pretoria
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Soweto
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Badalona
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 de 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 Univ. Gregorio Mara?on
city: Mataro / Barcelona
country: Spain
facility: C.A.P. Ronda Cerdanya
city: Mostoles / Madrid
country: Spain
facility: Hospital 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: 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
Study officials:
affiliation: BIL UK / Ireland
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: Neldam S, Edwards C. Long-term, open-label evaluation of the safety and efficacy of telmisartan 80 mg/hydrochlorothiazide 25 mg fixed-dose combination alone or with other antihypertensive medication. Expert Opin Pharmacother. 2009 Feb;10(3):345-52. doi: 10.1517/14656560802707937.