Clinical trial NCT00750113: Study Evaluating the Efficacy of Nifedipine GITS - Telmisartan Combination in Blood Pressure Control.
Official title: A Multicenter Study Evaluating the Efficacy of Nifedipine GITS - Telmisartan Combination in Blood Pressure Control and Beyond: Comparison of Two Treatment Strategies.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-09-10
Enrollment: 405
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients having uncontrolled or poorly controlled hypertension are at risk of experiencing cardiovascular events such as myocardial infarction or stroke. To reduce this risk an appropriate antihypertensive therapy should allow to reach a target blood pressure of less than 130/80 mmHg in order to maximise cardiovascular protection.The purpose of this study is to evaluate the efficacy in blood pressure control when anti-hypertensive therapy is initiated with a combination of low dose Nifedipine GITS and Telmisartan compared to a regimen starting with monotherapy before adding the other drug.The primary efficacy parameter will be the 24 hour mean systolic Blood Pressure on Ambulatory Blood Pressure Monitoring (ABPM) at 16 weeks of treatment compared to baseline


Eligibility criteria: Inclusion Criteria:

* Hypertension (office systolic blood pressure \> 135 mmHg), untreated or poorly controlled but stable antihypertensive regimen for \>/= 4 weeks
* Presence of type 2 diabetes mellitus or target organ damage (echocardiographic or electrocardiographic left ventricular hypertrophy or microalbuminuria)
* Presence of a metabolic syndrome, i.e at least two of the following \[(from letter (a) to letter(d)\] in patients with organ damage or at least one of the following \[from letter (b) to letter (d)\] in patients with diabetes mellitus: (a) impaired glucose tolerance (fasting plasma glucose 110 -125 mg/dl) (b )raised serum triglycerides (\>/= 150 mg/dl) or comitant use of statins for this indication(c) low HDL cholesterol (males: \< 40 mg/dl, females: \< 50 mg/dl)(d) waist circumference \>102 cm in men and \>88 cm in women
* Age: 18-75 years
* Negative pregnancy test in females
* Written informed consent

Exclusion Criteria:

* Concomitant treatment with AT1-antagonists e.g. losartan, eprosartan, telmisartan) or calcium-antagonists (e.g. amlodipine, felodipine, isradipine, nifedipine, nimodipine).
* Concomitant treatment with any other antihypertensive medication that cannot be safely withdrawn at entry (i.e taken on a stable regimen for \>/= 4 week) and that won't possibly be kept stable over the whole duration of the study.
* Concomitant treatment with known cytochrome P450-3A4 inhibitors (e.g cimetidine, anti-HIV protease inhibitors e.g. ritonavir, azole anti-mycotics eg. Ketoconazole, digoxin, quinidine, tacrolimus) or inducers such as anti-epileptic drugs (eg. phenytoin, carbamazepine and phenobarbitone) or rifampicin
* Concomitant treatment with potassium sparingdiuretics.
* Malignant, severe or labile essential hypertension, orthostatic hypotension
* Cardiovascular shock
* Evidence of secondary form of hypertension, including coarctation of the aorta, hyperaldosteronism, renal artery stenosis or pheochromocytoma
* Myocardial infarction or unstable angina within the previous 12 months
* Severe cardiac valve disease
* Severe rhythm or conduction disorder:
* Cerebrovascular ischaemic event (stroke, transient ischaemic attack) within the previous 12 months
* History of intra-cerebral haemorrhage or sub-arachnoid haemorrhage within the previous 12 months
* Type 1 diabetes mellitus
* Proteinuria (determined by uristix)
* BMI \> 34
* Uncorrected hypokalemia or hyperkalemia, potassium outside the range 3.0 to 5.5 mmol/l
* Sodium depletion and/or hypovolemia
* Gastrointestinal disease resulting in the potential for malabsorption)
* Liver disease or transaminase (AST, ALT) levels \> 3 x the upper limit of normal range.
* Renal failure, creatinine \>2.0 mg/dl
* General Exclusion Criteria: any malignant disease that has required treatment within the last five years, dementia or psychosis, history of non-compliance, alcoholism or drug abuse, treatment with any other investigational drug in the 30 days prior to entering the study, pregnancy and lactation, known state of allergy or hypersensitivity to nifedipine or any other dihydropyridine or to telmisartan, any surgical or medical condition which at the discretion of the investigator place the subject at higher risk from his/her participation in the study or are likely to prevent the subject from complying with the requirements of the study or completing the trial period, history of non compliance to medical regimens or subjects unwilling to comply with the study protocol.

Primary outcomes:
measure: The primary efficacy parameter will be the 24 hour mean systolic Blood Pressure on Ambulatory Blood Pressure Monitoring (ABPM)
timeFrame: at 16 weeks of treatment compared to baseline
Secondary outcomes:
measure: Office blood pressure, response rate (> 10mmHg decrease control rate (< 130/80) mean SBP, mean DBP.
timeFrame: 8, 16 weeks of treatment
measure: ABPM: % patients achieving BP < 125/80 mmHg morning BP increase/surge,24h mean diastolic BP,day average BP, night average BP,BP variability, pulse pressure through to peak ratio,smoothness index dipping or non dipping
timeFrame: 8, 16 and 24 weeks
measure: Microalbuminuria in subgroup (any reduction)
timeFrame: 8, 16 and 24 weeks
measure: Metabolic parameters: fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides
timeFrame: 8, 16 and 24 weeks
measure: Inflammatory markers: sRAGE (soluble receptors for advanced glycation end products) eotaxin-3, CRP (C-Reactive Protein)
timeFrame: 8, 16 and 24 weeks
Other outcomes:
Locations:
city: Pozzilli
country: Italy
state: Isernia
city: Monza
country: Italy
state: Monza-Brianza
city: Somma Lombardo
country: Italy
state: Varese
city: Ancona
country: Italy
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Broni
country: Italy
city: Catania
country: Italy
city: Cinisello Balsamo
country: Italy
city: Ferrara
country: Italy
city: L'Aquila
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Napoli
country: Italy
city: Novara
country: Italy
city: Padova
country: Italy
city: Palermo
country: Italy
city: Pavia
country: Italy
city: Perugia
country: Italy
city: Pisa
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Roma
country: Italy
city: Roma
country: Italy
city: Sassari
country: Italy
city: Siena
country: Italy
city: Siracusa
country: Italy
city: Treviso
country: Italy
city: Trieste
country: Italy
city: Varese
country: Italy
city: Venezia
country: Italy
city: Ferrol
country: Spain
state: A Coruña
city: Gijón
country: Spain
state: Asturias
city: Badalona
country: Spain
state: Barcelona
city: Jerez de la Frontera
country: Spain
state: Cádiz
city: Las Palmas de Gran Canaria
country: Spain
state: Las Palmas
city: Beniganim
country: Spain
state: Valencia
city: Badajoz
country: Spain
city: Ciudad Real
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Mancia G, Parati G, Bilo G, Choi J, Kilama MO, Ruilope LM; TALENT investigators. Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study. J Hypertens. 2011 Mar;29(3):600-9. doi: 10.1097/HJH.0b013e328342ef04.