HIGH Altitude CArdiovascular REsearch in the ANDES

Condition(s) targeted: Hypertension; High Altitude

Intervention: Telmisartan (Drug); Nifedipine (Drug); placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Istituto Auxologico Italiano

Official(s) and/or principal investigator(s):
Gianfranco Parati, MD, PhD, Principal Investigator, Affiliation: Istituto Auxologico Italiano

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.

Official title: HIGH Altitude CArdiovascular REsearch in the ANDES

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Effect of study treatment on 24 h ambulatory systolic blood pressure at high altitude

Secondary outcome:

Effect of study treatment on ambulatory blood pressure at high altitude (other variables)

Lake Louise Score

Effect of high altitude on ambulatory blood pressure

Effect of high altitude on conventional blood pressure

Effect of study treatment on conventional blood pressure at high altitude.

Rate of adverse events

Effect of study treatment on ambulatory heart rate at high altitude

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: 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)

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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

Universidad Peruana Cayetano Heredia, Lima, Peru

Starting date: May 2012
Last updated: April 9, 2013