HIGH Altitude CArdiovascular REsearch in the ANDES (HIGHCARE-A)
Primary Purpose
Hypertension, High Altitude
Status
Completed
Phase
Phase 4
Locations
Peru
Study Type
Interventional
Intervention
Telmisartan
Nifedipine
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypertension focused on measuring arterial hypertension, high altitude, hypobaric hypoxia, combination treatment, angiotensin receptor blocker, calcium antagonist
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
Sites / Locations
- Universidad Peruana Cayetano Heredia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Telmisartan/nifedipine
Placebo
Arm 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
Two tablets containing placebo daily in the morning
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Lake Louise Score
Differences in Lake Louise Score (score of acute mountain sickness severity) between groups
Effect of high altitude on ambulatory blood pressure
Change in ambulatory blood pressure between sea level condition and high altitude in both treatment groups
Effect of high altitude on conventional blood pressure
Change in conventional blood pressure between sea level condition and high altitude in both groups
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
Rate of adverse events
Differences in rate of adverse events between groups.
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
Full Information
NCT ID
NCT01830530
First Posted
February 18, 2013
Last Updated
April 9, 2013
Sponsor
Istituto Auxologico Italiano
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT01830530
Brief Title
HIGH Altitude CArdiovascular REsearch in the ANDES
Acronym
HIGHCARE-A
Official Title
HIGH Altitude CArdiovascular REsearch in the ANDES
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Auxologico Italiano
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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:
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, High Altitude
Keywords
arterial hypertension, high altitude, hypobaric hypoxia, combination treatment, angiotensin receptor blocker, calcium antagonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Telmisartan/nifedipine
Arm Type
Experimental
Arm 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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Two tablets containing placebo daily in the morning
Intervention Type
Drug
Intervention Name(s)
Telmisartan
Other Intervention Name(s)
Pritor, Micardis
Intervention 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
Intervention Type
Drug
Intervention Name(s)
Nifedipine
Other Intervention Name(s)
Adalat
Intervention 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
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
two tablets daily in the morning
Primary Outcome Measure Information:
Title
Effect of study treatment on 24 h ambulatory systolic blood pressure at high altitude
Description
Difference in 24 h ambulatory systolic BP at high altitude (Visit 4) between combination therapy group and placebo group
Time Frame
After 6 weeks of study treatment, during high altitude visit
Secondary Outcome Measure Information:
Title
Effect of study treatment on ambulatory blood pressure at high altitude (other variables)
Description
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
Time Frame
After 6 weeks of study treatment, during high altitude visit
Title
Lake Louise Score
Description
Differences in Lake Louise Score (score of acute mountain sickness severity) between groups
Time Frame
After 6 weeks of study treatment, during high altitude visit
Title
Effect of high altitude on ambulatory blood pressure
Description
Change in ambulatory blood pressure between sea level condition and high altitude in both treatment groups
Time Frame
After 6 weeks of study treatment, during high altitude visit
Title
Effect of high altitude on conventional blood pressure
Description
Change in conventional blood pressure between sea level condition and high altitude in both groups
Time Frame
After 6 weeks of study treatment, during high altitude visit
Title
Effect of study treatment on conventional blood pressure at high altitude.
Description
Difference in conventional systolic and diastolic blood pressure at high altitude (Visit 4) between combination therapy group and placebo group
Time Frame
After 6 weeks of study treatment, during high altitude visit
Title
Rate of adverse events
Description
Differences in rate of adverse events between groups.
Time Frame
After 6 weeks of treatment plus up to 1 additional week of treatment needed for high altitude visit (study end).
Title
Effect of study treatment on ambulatory heart rate at high altitude
Description
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
Time Frame
After 6 weeks of study treatment, during high altitude visit
Other Pre-specified Outcome Measures:
Title
Differences in other variables assessed in the study at high altitude between treatment groups
Description
Differences between treatment groups in polysomnographic data, arterial stiffness, blood tests, echocardiography data assessed at high altitude
Time Frame
high altitude visit ( Visit 4)
Title
blood pressure response at sea level
Description
Changes in polysomnographic data, arterial stiffness, blood tests, echocardiography data between sea level condition and high altitude
Time Frame
Sea level visit (3) and high altitude visit (4)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gianfranco Parati, MD, PhD
Organizational Affiliation
Istituto Auxologico Italiano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universidad Peruana Cayetano Heredia
City
Lima
Country
Peru
12. IPD Sharing Statement
Citations:
PubMed Identifier
29886423
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.
Results Reference
derived
PubMed Identifier
25895588
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.
Results Reference
derived
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HIGH Altitude CArdiovascular REsearch in the ANDES
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