HIGH Altitude CArdiovascular REsearch in the ANDES (HIGHCARE-A)

Istituto Auxologico Italiano

Status and phase: Completed; Phase 4

Conditions: Hypertension; High Altitude

Treatments: Drug: placebo; Drug: Nifedipine; Drug: Telmisartan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01830530

09F102

Details and patient eligibility

About

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.

Full 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:

1. to assess the response of BP to high altitude exposure in hypertensive subjects residing at sea level
2. 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)

Enrollment: 100 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

Telmisartan/nifedipine

Experimental group

Description:

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

Treatment:

Drug: Telmisartan

Drug: Nifedipine

Placebo

Placebo Comparator group

Description:

Two tablets containing placebo daily in the morning

Treatment:

Drug: placebo