HIGH Altitude CArdiovascular REsearch in the ANDES

Hypertension Clinical Trial

— HIGHCARE-A  

Official title:

HIGH Altitude CArdiovascular REsearch in the ANDES

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01830530
• Other study ID #: 09F102
• Status: Completed
• Phase: Phase 4
• First received: February 18, 2013
• Last updated: April 9, 2013
• Start date: May 2012
• Est. completion date: October 2012

Study information

• Verified date: February 2013
• Source: Istituto Auxologico Italiano
• Contact: n/a
• Is FDA regulated: No
• Health authority: Peru: Instituto Nacional de SaludPeru: General Directorate of Pharmaceuticals, Devices, and Drugs
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: October 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Altitude Sickness
• High Altitude
• Hypertension

Intervention

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
• 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
• placebo
two tablets daily in the morning

Locations

Country	Name	City	State
Peru	Universidad Peruana Cayetano Heredia	Lima

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Auxologico Italiano	Bayer

Country where clinical trial is conducted

Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences in other variables assessed in the study at high altitude between treatment groups	Differences between treatment groups in polysomnographic data, arterial stiffness, blood tests, echocardiography data assessed at high altitude	high altitude visit ( Visit 4)	No
Other	blood pressure response at sea level	Changes in polysomnographic data, arterial stiffness, blood tests, echocardiography data between sea level condition and high altitude	Sea level visit (3) and high altitude visit (4)	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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).	Yes
Secondary	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	No