Clinical trial NCT01830530: HIGH Altitude CArdiovascular REsearch in the ANDES
Official title: HIGH Altitude CArdiovascular REsearch in the ANDES
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
High Altitude
Keywords: arterial hypertension
high altitude
hypobaric hypoxia
combination treatment
angiotensin receptor blocker
calcium antagonist
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2013-04-12
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Eligibility 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

Primary outcomes:
measure: Effect of study treatment on 24 h ambulatory systolic blood pressure at high altitude
timeFrame: After 6 weeks of study treatment, during high altitude visit
Secondary outcomes:
measure: Effect of study treatment on ambulatory blood pressure at high altitude (other variables)
timeFrame: After 6 weeks of study treatment, during high altitude visit
measure: Lake Louise Score
timeFrame: After 6 weeks of study treatment, during high altitude visit
measure: Effect of high altitude on ambulatory blood pressure
timeFrame: After 6 weeks of study treatment, during high altitude visit
measure: Effect of high altitude on conventional blood pressure
timeFrame: After 6 weeks of study treatment, during high altitude visit
measure: Effect of study treatment on conventional blood pressure at high altitude.
timeFrame: After 6 weeks of study treatment, during high altitude visit
measure: Rate of adverse events
timeFrame: After 6 weeks of treatment plus up to 1 additional week of treatment needed for high altitude visit (study end).
measure: Effect of study treatment on ambulatory heart rate at high altitude
timeFrame: After 6 weeks of study treatment, during high altitude visit
Other outcomes:
measure: Differences in other variables assessed in the study at high altitude between treatment groups
timeFrame: high altitude visit ( Visit 4)
measure: blood pressure response at sea level
timeFrame: Sea level visit (3) and high altitude visit (4)
Locations:
city: Lima
country: Peru
facility: Universidad Peruana Cayetano Heredia
Study officials:
affiliation: Istituto Auxologico Italiano
name: Gianfranco Parati, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Caravita S, Faini A, Baratto C, Bilo G, Macarlupu JL, Lang M, Revera M, Lombardi C, Villafuerte FC, Agostoni P, Parati G. Upward Shift and Steepening of the Blood Pressure Response to Exercise in Hypertensive Subjects at High Altitude. J Am Heart Assoc. 2018 Jun 9;7(12):e008506. doi: 10.1161/JAHA.117.008506.
citation: Bilo G, Villafuerte FC, Faini A, Anza-Ramirez C, Revera M, Giuliano A, Caravita S, Gregorini F, Lombardi C, Salvioni E, Macarlupu JL, Ossoli D, Landaveri L, Lang M, Agostoni P, Sosa JM, Mancia G, Parati G. Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study. Hypertension. 2015 Jun;65(6):1266-72. doi: 10.1161/HYPERTENSIONAHA.114.05003. Epub 2015 Apr 20.