HIGHCARE-A: HIGH Altitude CArdiovascular REsearch in the ANDES

Sponsor

Istituto Auxologico Italiano (Other)

Overall Status

Completed

CT.gov ID

NCT01830530

Collaborator

Bayer (Industry)

100

Enrollment

Location

Arms

Duration (Months)

19.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is aimed to assess the efficacy of combined treatment with two antihypertensive agents (telmisartan and nifedipine) in subjects with mild hypertension exposed to high altitude.

Condition or Disease	Intervention/Treatment	Phase
Hypertension High Altitude	Drug: Telmisartan Drug: Nifedipine Drug: placebo	Phase 4

Detailed Description

This is a parallel group, prospective, double-blind, placebo controlled randomized trial, comparing the effects of combination of two antihypertensive agents (telmisartan/nifedipine)with placebo in hypertensive subjects exposed to high altitude. The principal objectives are:

to assess the response of BP to high altitude exposure in hypertensive subjects residing at sea level
To assess the efficacy and safety of combination of telmisartan 80 mg with nifedipine GITS 30 mg in preventing a possible excessive BP increase in hypertensive subjects exposed to high altitude.

The following data will be collected during the study at the different steps:

Clinical history
Symptoms and adverse events questionnaire
Conventional BP and heart rate (HR) measurement - seated measurements with a validated oscillometric device will be performed after at least 5 minutes rest on non-dominant arm; two measurements will be performed 1-2 minutes apart and their average will be used in the analyses
Vital signs:

respiratory rate - will be measured manually over 60 seconds body height and weight, waist circumference blood oxygen saturation (SpO2)

Lake Louise Score
24 h ambulatory blood pressure monitoring (ABPM; AND TM2430, AND, Japan)
Echocardiography
Arterial properties assessment
Six minute walking test (6MWT)
Cardiopulmonary Exercise Test (CPET) in a subgroup of subjects
Polysomnography with a portable device
Pulmonary function tests (only at sea level baseline visit)
Fluid balance chart
Blood and urine analyses: Visit 1: electrolytes, creatinine, estimated glomerular filtration rate (eGFR), glycemia, renin, angiotensin, aldosterone, plasma catecholamines, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 randomly selected subjects), samples for genetic studies. Visit 2: electrolytes, creatinine, eGFR. Visit 3: complete blood count, electrolytes, creatinine, eGFR, glycemia, insulin, renin, angiotensin, aldosterone, plasma catecholamines, classic urinalysis, microalbuminuria, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 subjects selected at Visit 1). Visit 4: electrolytes, creatinine, eGFR, glycemia, insulin, renin, angiotensin, aldosterone, plasma catecholamines, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 subjects selected at Visit 1)

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

HIGH Altitude CArdiovascular REsearch in the ANDES

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Telmisartan/nifedipine Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination	Drug: Telmisartan Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination Other Names: Pritor Micardis Drug: Nifedipine Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination Other Names: Adalat
Placebo Comparator: Placebo Two tablets containing placebo daily in the morning	Drug: placebo two tablets daily in the morning

Arm

Intervention/Treatment

Experimental: Telmisartan/nifedipine

Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination

Drug: Telmisartan

Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination

Other Names:

Pritor

Micardis

Drug: Nifedipine

Subjects treated with telmisartan 80 mg (1 capsule daily in the morning) plus nifedipine slow release 30 mg (1 capsule daily in the morning) combination

Other Names:

Adalat

Placebo Comparator: Placebo

Two tablets containing placebo daily in the morning

Drug: placebo

two tablets daily in the morning

Outcome Measures

Primary Outcome Measures

Effect of study treatment on 24 h ambulatory systolic blood pressure at high altitude [After 6 weeks of study treatment, during high altitude visit]
Difference in 24 h ambulatory systolic BP at high altitude (Visit 4) between combination therapy group and placebo group

Secondary Outcome Measures

Effect of study treatment on ambulatory blood pressure at high altitude (other variables) [After 6 weeks of study treatment, during high altitude visit]
Differences in other ambulatory blood pressure (BP) variables (including 24 h diastolic BP, daytime and night-time BP, nocturnal fall of BP) at high altitude (V4) between combination therapy and placebo groups
Lake Louise Score [After 6 weeks of study treatment, during high altitude visit]
Differences in Lake Louise Score (score of acute mountain sickness severity) between groups
Effect of high altitude on ambulatory blood pressure [After 6 weeks of study treatment, during high altitude visit]
Change in ambulatory blood pressure between sea level condition and high altitude in both treatment groups
Effect of high altitude on conventional blood pressure [After 6 weeks of study treatment, during high altitude visit]
Change in conventional blood pressure between sea level condition and high altitude in both groups
Effect of study treatment on conventional blood pressure at high altitude. [After 6 weeks of study treatment, during high altitude visit]
Difference in conventional systolic and diastolic blood pressure at high altitude (Visit 4) between combination therapy group and placebo group
Rate of adverse events [After 6 weeks of treatment plus up to 1 additional week of treatment needed for high altitude visit (study end).]
Differences in rate of adverse events between groups.
Effect of study treatment on ambulatory heart rate at high altitude [After 6 weeks of study treatment, during high altitude visit]
Differences in ambulatory heart rate (HR) variables (including 24 h, daytime and night-time HR, and nocturnal fall of HR) at high altitude (V4) between combination therapy and placebo groups

Other Outcome Measures

Differences in other variables assessed in the study at high altitude between treatment groups [high altitude visit ( Visit 4)]
Differences between treatment groups in polysomnographic data, arterial stiffness, blood tests, echocardiography data assessed at high altitude
blood pressure response at sea level [Sea level visit (3) and high altitude visit (4)]
Changes in polysomnographic data, arterial stiffness, blood tests, echocardiography data between sea level condition and high altitude

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Permanent residence at low (<500 m) altitude
Conventional systolic BP (average of two measurements) 140-159 mmHg or conventional diastolic BP 90-99 mmHg in subjects untreated or after 4 weeks of washout
Mean daytime systolic BP ≥135 and <150 mmHg and/or mean daytime diastolic BP ≥85 and <95 mmHg in subjects untreated or after 4 weeks of washout
Written informed consent to participate in the study

Exclusion Criteria:

Conventional systolic BP (average of two measurements) ≥150 mmHg and conventional diastolic BP ≥95 mmHg in treated subjects
Regular use of two or more antihypertensive drugs (with the exception of subjects on two antihypertensive drugs in low doses)
Treated antihypertensive subjects in whom withdrawal of treatment is deemed unethical by the investigator (e.g. because of the existence of compelling indications other than hypertension for continuous use of previously used antihypertensive agent)
Contraindications (including a history of adverse reactions) to angiotensin receptor blockers or calcium antagonists
History of serious mountain sickness
Subjects who over 3 months preceding inclusion in the study spent considerable (> 1 week) amount of time at altitudes above 2500 m.
Cardiovascular diseases other than hypertension (coronary heart disease, heart failure, atrial fibrillation, valvular or congenital heart disease, cardiomyopathies, cerebrovascular disease, peripheral artery disease, aortic aneurysm)
Suspected or confirmed secondary hypertension
Diabetes mellitus
Serious respiratory disorders
Other conditions deemed relevant by the investigator (including liver disease, renal disease, thyroid disorders)
BMI ≥35 kg/m2
Upper arm circumference >32 cm
known severe obstructive sleep apnea (apnea-hypopnea index > 30 or use of CPAP) or excessive daytime sleepiness (Epworth Sleepiness Scale > 10)
Pregnancy
Premenopausal women not using effective contraceptive methods
Elevated probability of noncompliance with the study procedures