HIGH Altitude CArdiovascular REsearch in the ANDES

Study Overview
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Brief Summary
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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.

Detailed Description
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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)

Official Title
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HIGH Altitude CArdiovascular REsearch in the ANDES

Conditions
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Hypertension, High Altitude

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Nifedipine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan/nifedipine<br>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<br>* 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<br>* Other names: Micardis;Drug: Nifedipine<br>* 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<br>* Other names: Adalat;|
| Placebo Comparator: Placebo<br>Two tablets containing placebo daily in the morning | Drug: placebo<br>* two tablets daily in the morning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of study treatment on 24 h ambulatory systolic blood pressure at high altitude | Difference in 24 h ambulatory systolic BP at high altitude (Visit 4) between combination therapy group and placebo group | After 6 weeks of study treatment, during high altitude visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of study treatment on ambulatory blood pressure at high altitude (other variables) | 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 | After 6 weeks of study treatment, during high altitude visit | 
| Lake Louise Score | Differences in Lake Louise Score (score of acute mountain sickness severity) between groups | After 6 weeks of study treatment, during high altitude visit | 
| Effect of high altitude on ambulatory blood pressure | Change in ambulatory blood pressure between sea level condition and high altitude in both treatment groups | After 6 weeks of study treatment, during high altitude visit | 
| Effect of high altitude on conventional blood pressure | Change in conventional blood pressure between sea level condition and high altitude in both groups | After 6 weeks of study treatment, during high altitude visit | 
| Effect of study treatment on conventional blood pressure at high altitude. | Difference in conventional systolic and diastolic blood pressure at high altitude (Visit 4) between combination therapy group and placebo group | After 6 weeks of study treatment, during high altitude visit | 
| Rate of adverse events | Differences in rate of adverse events between groups. | After 6 weeks of treatment plus up to 1 additional week of treatment needed for high altitude visit (study end). | 
| Effect of study treatment on ambulatory heart rate at high altitude | 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 | After 6 weeks of study treatment, during high altitude visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arterial hypertension, high altitude, hypobaric hypoxia, combination treatment, angiotensin receptor blocker, calcium antagonist