HypoxiaPhase 4NCT00924833

Effects of Nebivolol Versus Carvedilol on Cardiopulmonary Function at High Altitude in Healthy Subjects.

A Phase 4 study testing Carvedilol and Nebivolol in people with Hypoxia and Altitude, run by Istituto Auxologico Italiano at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Hypoxia, Altitude, Heart Failure
What is being tested?: Carvedilol and Nebivolol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 1 siteItaly
Study dates: May 2006to Nov 2006
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Men or women of any racial background
healthy
sealevel resident
age >= 18 years, =< 65 years
SBP< 130 mmHg and DBP< 80 mmHg, average of two measures at the sceening visit
FG < 100 mg/dl (5.6 mmol/l)
BMI < 25
written informed consent signed

Who cannot join

engagement in regular exercise training
smoking habit
being enrolled in another research study
any current or previous cardiovascular, metabolic disease or any other cronic disease
any current treatment for any medical condition
any medical condition preventing or contraindication exposure to altitude hypoxia

Show all 14Show fewer

any gastrointestinal disorder interfering with drug absorption
known allergy or contraindications to beta-blockers
pregnant or lactating women; women in reproductive age not using recognized contraceptive methods.
malignancy within the last 5 years
drug abuse or alcohol abuse within the last 5 years
history of noncompliance to medical regimens
incapacity or unwillingness to sign the informed consent
participation in any investigational clinical trial within the last 3 months

Trial locations and contacts

1 site in 1 country.

Italy1 site

Laboratorio Ricerche Cardiologiche. Istituto Auxologico Italiano. Ospedale S. Luca. Via Spagnoletto, 3. Regina Margherita Hut (Monte Rosa, Italian Alps, 4559 m)
Milan, 20148

Other trials in Italy

About this study

Official title: Comparison of the Cardiovascular, Metabolic and Respiratory Effects of Nebivolol and Carvedilol at High Altitude in Healthy Subjects.

Exposure of healthy subjects to high altitude hypoxia elicits changes in cardiovascular, respiratory and metabolic features as weel as in exercise performance similar, for some aspects, to those observed in chronic heart failure. Exposure to high altitude hypoxia represents a suitable model to assess different treatments proposed for this pathological condition. Our aim was to evaluate the impact of two different third-generation beta-blockers used in heart failure (carvedilol and nebivolol) on cardiovascular, respiratory, metabolic profile and on exercise performance at high altitude.

Read the detailed description

Methods. Study Subjects. Adults, males and females, non smoking healthy volunteers, sea-level residents not engaged in regular endurance exercise training, taking no medications will be recruited. As there are no studies comparing the effects of beta-blockers on exercise performance at high altitude, the sample size set for each treatment arm was defined on the basis of the sample size of previous investigations showing significant changes in exercise performance in normal subjects taking no medications.

Study design. Time 0. Screening, enrollement and randomization. Subjects meeting the inclusion/exclusion criteria will undergo at sea-level, general laboratory investigations and physical examination. Eligible subjects will be double blindly randomized to either placebo (one tablet twice daily), carvedilol (one 25 mg tablets twice daily), or to nebivolol (one 5 mg tablet in the morning and one placebo tablet in the evening).

Time 1. Before starting the medications, at sea level after an overnight fast, subject will undergo: blood pressure and heart rate measurement, 24 hour ambulatory blood pressure monitoring, Doppler heart ultrasound, cardiopulmonary exercise test, resting energy expenditure measurement.

Time 2. After three weeks of allocated treatment, at sea-level, after an overnight fast, subjects will undergo: blood pressure and heart rate measurement, 24 hour ambulatory blood pressure monitoring, Doppler heart ultrasound, cardiopulmonary exercise test, resting energy expenditure measurement.

Time 3. Under treatment within the first two days of high altitude exposure (Regina Margherita hut, Monte Rosa, altitude 4559 m), subjects will undergo after an overnight fast to blood pressure and heart rate measurement, 24 hour ambulatory blood pressure monitoring, Doppler heart ultrasound, cardiopulmonary exercise test, resting energy expenditure measurement, acute mountain sickness quantification by the Lake Louise Score.

Protocol for blood pressure and heart rate measurement. Blood pressure and heart rate were measured according to current European guidelines(Task Force for the Management of Arterial Hypertension of the European Society of Hypertension(ESH) and of the European Society of Cardiology (ESC). 2007 Guidelines for the Management of Arterial Hypertension. J Hypertens 2007; 25:1105-1187.
Protocol for 24 hour ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring was performed according to current European guidelines(O'Brien E, et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens 2005; 23: 1697-701).
Protocol for Doppler heart ultrasound. All echographic-Doppler examinations will be performed by the same two operators using a portable device (Vivid I, GE Ultrasound) according to current guidelines (Lang RM, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006; 7 : 79-108
Protocol for cardiopulmonary exercise test. Tests will be performed and evaluated according to current European Society of Cardiology guidelines (Eur J Cardiovasc Prev Rehabil 13:150-164 2006; Eur J Cardiovasc Prev Rehabil 2006; 13:300-311). All tests will be performed using the same cyclo-ergometer (Ergometrics 100, Ergoline, Bitz, Germany)and metabolic cart (Oxycon Mobile software v. 4.6, VIASYS Healthcare GmbH, Wurburg, Germany). The exercise protocol will include 10 minutes of monitored sitting rest, followed by 3 minutes of unloaded pedalling and by 30 W load increments every 2 minutes up to exhaustion. Breath-by-breath ventilation, respiratory gases, one-lead ECG and pulse oxymetry (SpO2) will be recorded throughout each test. Arterial blood pressure will be measured by a mercury sphygmomanometer in duplicate at the end of the resting phase and of each 30 W step, and at peak exercise. Cardiopulmonry exercise tests will be blindly and independently evaluated by two expert readers. The anaerobic threshold will be identified by the standard technique (Wasserman K. Breathing during exercise. N Engl J Med 1978; 298:780-785. VE/VCO2 slope will be calculated as the slope of the linear relationship between VE and VCO2 measured up to the respiratory compensation point.
Protocol for resting energy expenditure measurement. The energy expenditure was calculated according to the abbreviated formula provided by Weir (Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol Lond 1949; 55:14-21). O2 consumption and CO2 production (integrated over 1 min) were measured for 30 min. Baseline values were calculated by averaging the readings taken during the last 10 min.
Protocol for assessment of acute mountain sickness. Acute mountain sickness (AMS) will be assessed by means of the Lake Louise AMS Scoring system (Roach RC, Bärtsch P et al. The Lake Louise AMS Scoring Consensus Committee. The Lake Louise acute mountain sickness scoring system. In: Sutton JR, Houtson CS, Coates G, eds. Hypoxia and Molecular Medicine. Burlington, VT: Queen City Printers; 1993:272-274).
Statistical analysis. Data will be reported as means ± SD. Data management and analysis will be performed with SPSS version 13.0 (SPSS Inc, Chicago, IL, USA). Differences among groups, changes over time within each group (time effect), and any interaction (differing trends over time among groups), will be assessed by two-way repeated measures ANOVA with unpaired Student's t-test with Bonferroni correction whenever needed. For all parameters during cardiopulmonary exercise test, mean values will be computed over 20 seconds. Spearman correlations will be used to assess the relationship between peak VO2 and other respiratory and haemodynamic variables at altitude. A P level of < 0.05 was considered statistically significant.

Conditions: Hypoxia, Altitude, Heart Failure
Being tested: placebo, Carvedilol, Nebivolol
Keywords: hypoxia, autonomic nervous system, blood pressure, heart rate, exercise, heart failure, receptors, adrenergic, beta.
Medical subject headings: Hypoxia, Heart Failure, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

placeboDrug
placebo tablet BID
CarvedilolDrug
Carvedilol 25 mg tablets. One tablet twice daily.
NebivololDrug
nebivolol 5 mg tablets. One nebivolol tablet daily. One placebo tablet daily.

Study groups in NCT00924833
Study group	Role	What they receive
placebo	Placebo comparator	Placebo tablets. One tablet twice daily. Receives: Drug: placebo
2: Carvedilol	Active comparator	Carvedilol 25 mg tablets. One tablet twice daily. Receives: Drug: Carvedilol
3: Nebivolol	Active comparator	Nebivolol 5 mg tablets. One nebivolo tablet daily. One placebo tablet daily. Receives: Drug: Nebivolol

What is being measured

The primary outcome is the main question the study is designed to answer.

Peak Exercise Oxygen Consumption
Oxygen consumption at peak of exercise
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3
Difference in peak exercise oxygen consumption between Time 1 and Time 3 (Time 3 - Time 1)
Measured: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Peak Exercise Minute Ventilation
Minute ventilation at peak of exercise. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min)
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.
Difference in peak exercise minute ventilation between Time 1 and Time 3 (Time 3 - Time 1.
Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min).
Measured: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.

Secondary outcomes (5)

Peak Exercise Oxygen Saturation
Oxygen saturation by pulse oxymetry at peak of exercise
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Systolic Pulmonary Artery Pressure.
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Resting Energy Expenditure
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Sitting Blood Pressure and Heart Rate
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Mean 24 Hour/Daytime/Night-time Blood Pressure and Heart Rate
Measured: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2006Nov 2006

First posted19 Jun 2009 (estimated)
Study startMay 2006
Primary completionNov 2006
Study completionNov 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for HypoxiaStudies of the same condition, open and under way.
More trials run by Istituto Auxologico ItalianoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00924833
Sponsor's protocol ID: 09F602
Status last verified: Feb 2009
First submitted: 19 Feb 2009
Last updated: 2 Sep 2009
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Modesti PA, Vanni S, Morabito M, Modesti A, Marchetta M, Gamberi T, Sofi F, Savia G, Mancia G, Gensini GF, Parati G. Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study. Circulation. 2006 Sep 26;114(13):1410-6. doi: 10.1161/CIRCULATIONAHA.105.605527. Epub 2006 Sep 18.
PubMed 16982943
Agostoni P, Contini M, Magini A, Apostolo A, Cattadori G, Bussotti M, Veglia F, Andreini D, Palermo P. Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia. Eur J Heart Fail. 2006 Nov;8(7):729-35. doi: 10.1016/j.ejheart.2006.02.001. Epub 2006 Mar 13.
PubMed 16533619
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available.
PubMed 17563527
O'Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P; European Society of Hypertension Working Group on Blood Pressure Monitoring. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens. 2005 Apr;23(4):697-701. doi: 10.1097/01.hjh.0000163132.84890.c4. No abstract available.
PubMed 15775768
Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W; American Society of Echocardiography's Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr. 2006 Mar;7(2):79-108. doi: 10.1016/j.euje.2005.12.014. Epub 2006 Feb 2.
PubMed 16458610
Task Force of the Italian Working Group on Cardiac Rehabilitation Prevention; Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corra U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Apr;13(2):150-64. doi: 10.1097/01.hjr.0000209812.05573.04.
PubMed 16575267
Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention (Gruppo Italiano di Cardiologia Riabilitativa e Prevenzione, GICR); Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corra U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Jun;13(3):300-11. doi: 10.1097/00149831-200606000-00003.
PubMed 16926657
WEIR JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949 Aug;109(1-2):1-9. doi: 10.1113/jphysiol.1949.sp004363. No abstract available.
PubMed 15394301

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 2 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparison of the Cardiovascular, Metabolic and Respiratory Effects of Nebivolol and Carvedilol at High Altitude in Healthy Subjects.
ClinicalTrials.gov ID: NCT00924833
Acronym / sponsor ID: 09F602
Conditions: Hypoxia, Altitude, Heart Failure
Keywords: hypoxia, autonomic nervous system, blood pressure, heart rate, exercise, heart failure, receptors, adrenergic, beta.
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Istituto Auxologico ItalianoUniversity, hospital or other
Collaborators: Menarini Group
Study start: May 2006
Primary completion: Nov 2006 (actual)
Study completion: Nov 2006 (actual)
First posted: 19 Jun 2009 (estimated)
Results: Posted 19 Jun 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Protocol for blood pressure and heart rate measurement. Blood pressure and heart rate were measured according to current European guidelines(Task Force for the Management of Arterial Hypertension of the European Society of Hypertension(ESH) and of the European Society of Cardiology (ESC). 2007 Guidelines for the Management of Arterial Hypertension. J Hypertens 2007; 25:1105-1187.
Protocol for 24 hour ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring was performed according to current European guidelines(O'Brien E, et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens 2005; 23: 1697-701).
Protocol for Doppler heart ultrasound. All echographic-Doppler examinations will be performed by the same two operators using a portable device (Vivid I, GE Ultrasound) according to current guidelines (Lang RM, et al. Recommendations for chamber quantification. Eur J Echocardiogr 2006; 7 : 79-108
Protocol for cardiopulmonary exercise test. Tests will be performed and evaluated according to current European Society of Cardiology guidelines (Eur J Cardiovasc Prev Rehabil 13:150-164 2006; Eur J Cardiovasc Prev Rehabil 2006; 13:300-311). All tests will be performed using the same cyclo-ergometer (Ergometrics 100, Ergoline, Bitz, Germany)and metabolic cart (Oxycon Mobile software v. 4.6, VIASYS Healthcare GmbH, Wurburg, Germany). The exercise protocol will include 10 minutes of monitored sitting rest, followed by 3 minutes of unloaded pedalling and by 30 W load increments every 2 minutes up to exhaustion. Breath-by-breath ventilation, respiratory gases, one-lead ECG and pulse oxymetry (SpO2) will be recorded throughout each test. Arterial blood pressure will be measured by a mercury sphygmomanometer in duplicate at the end of the resting phase and of each 30 W step, and at peak exercise. Cardiopulmonry exercise tests will be blindly and independently evaluated by two expert readers. The anaerobic threshold will be identified by the standard technique (Wasserman K. Breathing during exercise. N Engl J Med 1978; 298:780-785. VE/VCO2 slope will be calculated as the slope of the linear relationship between VE and VCO2 measured up to the respiratory compensation point.
Protocol for resting energy expenditure measurement. The energy expenditure was calculated according to the abbreviated formula provided by Weir (Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol Lond 1949; 55:14-21). O2 consumption and CO2 production (integrated over 1 min) were measured for 30 min. Baseline values were calculated by averaging the readings taken during the last 10 min.
Protocol for assessment of acute mountain sickness. Acute mountain sickness (AMS) will be assessed by means of the Lake Louise AMS Scoring system (Roach RC, Bärtsch P et al. The Lake Louise AMS Scoring Consensus Committee. The Lake Louise acute mountain sickness scoring system. In: Sutton JR, Houtson CS, Coates G, eds. Hypoxia and Molecular Medicine. Burlington, VT: Queen City Printers; 1993:272-274).
Statistical analysis. Data will be reported as means ± SD. Data management and analysis will be performed with SPSS version 13.0 (SPSS Inc, Chicago, IL, USA). Differences among groups, changes over time within each group (time effect), and any interaction (differing trends over time among groups), will be assessed by two-way repeated measures ANOVA with unpaired Student's t-test with Bonferroni correction whenever needed. For all parameters during cardiopulmonary exercise test, mean values will be computed over 20 seconds. Spearman correlations will be used to assess the relationship between peak VO2 and other respiratory and haemodynamic variables at altitude. A P level of < 0.05 was considered statistically significant.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
placebo	Placebo comparator	Drug: placeboPlacebo tablets. One tablet twice daily.
2: Carvedilol	Active comparator	Drug: CarvedilolCarvedilol 25 mg tablets. One tablet twice daily.
3: Nebivolol	Active comparator	Drug: NebivololNebivolol 5 mg tablets. One nebivolo tablet daily. One placebo tablet daily.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Men or women of any racial background
healthy
sealevel resident
age >= 18 years, =< 65 years
SBP< 130 mmHg and DBP< 80 mmHg, average of two measures at the sceening visit

Key exclusion criteria (14 listed)

engagement in regular exercise training
smoking habit
being enrolled in another research study
any current or previous cardiovascular, metabolic disease or any other cronic disease
any current treatment for any medical condition

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
placeboplacebo tablet BID	Drug	placebo
CarvedilolCarvedilol 25 mg tablets. One tablet twice daily.	Drug	2: Carvedilol
Nebivololnebivolol 5 mg tablets. One nebivolol tablet daily. One placebo tablet daily.	Drug	3: Nebivolol

Primary outcome

Peak Exercise Oxygen Consumption
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Oxygen consumption at peak of exercise
Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3
Time frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Difference in peak exercise oxygen consumption between Time 1 and Time 3 (Time 3 - Time 1)
Peak Exercise Minute Ventilation
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Minute ventilation at peak of exercise. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min)
Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.
Time frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Difference in peak exercise minute ventilation between Time 1 and Time 3 (Time 3 - Time 1. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min).

5 secondary outcomes

Peak Exercise Oxygen Saturation
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Systolic Pulmonary Artery Pressure.
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Resting Energy Expenditure
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Sitting Blood Pressure and Heart Rate
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.
Mean 24 Hour/Daytime/Night-time Blood Pressure and Heart Rate
Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.

Results and safety

Results posted to the registry on 19 Jun 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	9	9
Carvedilol	9	9
Nebivolol	9	9

Primary outcome: Peak Exercise Oxygen Consumption

Time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.. Mean (Standard Deviation). Unit: ml/Kg/min

Measure	Placebo n = 7	Carvedilol n = 8	Nebivolol n = 8
Time 1	33.9 (10.4)	37.6 (4.3)	38.0 (8.7)
Time 2	33.9 (9.4)	36.2 (3.9)	39.7 (8.6)
Time 3	22.9 (8.7)	24.0 (4.1)	28.8 (5.1)

Placebo vs Carvedilol vs Nebivolol: p = 0.01, ANOVA

Primary outcome: Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3

Time frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.. Mean (Standard Deviation). Unit: ml/Kg/min

Measure	Placebo n = 9	Carvedilol n = 9	Nebivolol n = 9
Value	-32.7 (11)	-37.6 (8.2)	-22.5 (8)

Placebo vs Carvedilol vs Nebivolol: p <0.05, ANOVA

Primary outcome: Peak Exercise Minute Ventilation

Measure	Placebo n = 7	Carvedilol n = 8	Nebivolol n = 8
Time 1	93.9 (29.1)	90.3 (21.8)	81.8 (24.4)
Time 2	95.6 (29.9)	89.6 (22.2)	83.8 (25.2)
Time 3	90.3 (19.9)	84.5 (27.4)	92.0 (20.7)

Placebo vs Carvedilol vs Nebivolol: p = 0.93, ANOVA

Primary outcome: Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.

Time frame: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.. Mean (Standard Deviation). Unit: L/min

Measure	Placebo n = 7	Carvedilol n = 8	Nebivolol n = 8
Value	0.7 (20.2)	-9.3 (13.3)	15.2 (17.1)

Placebo vs Carvedilol vs Nebivolol: p <0.05, ANOVA

5 secondary outcomes are reported in the full results.

Limitations and caveats (from the sponsor): We used standard doses of both beta blockers and observed similar HR reductions. We could not individually titrate drug doses. The degree of beta blockade might have been different in each subject.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2009.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16982943Modesti PA, Vanni S, Morabito M, Modesti A, Marchetta M, Gamberi T, Sofi F, Savia G, Mancia G, Gensini GF, Parati G. Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study. Circulation. 2006 Sep 26;114(13):1410-6. doi: 10.1161/CIRCULATIONAHA.105.605527. Epub 2006 Sep 18.
Background: PubMed 16533619Agostoni P, Contini M, Magini A, Apostolo A, Cattadori G, Bussotti M, Veglia F, Andreini D, Palermo P. Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia. Eur J Heart Fail. 2006 Nov;8(7):729-35. doi: 10.1016/j.ejheart.2006.02.001. Epub 2006 Mar 13.
Background: PubMed 17563527Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007 Jun;25(6):1105-87. doi: 10.1097/HJH.0b013e3281fc975a. No abstract available.
Background: PubMed 15775768O'Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, Myers M, Padfield P, Palatini P, Parati G, Pickering T, Redon J, Staessen J, Stergiou G, Verdecchia P; European Society of Hypertension Working Group on Blood Pressure Monitoring. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens. 2005 Apr;23(4):697-701. doi: 10.1097/01.hjh.0000163132.84890.c4. No abstract available.
Background: PubMed 16458610Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W; American Society of Echocardiography's Nomenclature and Standards Committee; Task Force on Chamber Quantification; American College of Cardiology Echocardiography Committee; American Heart Association; European Association of Echocardiography, European Society of Cardiology. Recommendations for chamber quantification. Eur J Echocardiogr. 2006 Mar;7(2):79-108. doi: 10.1016/j.euje.2005.12.014. Epub 2006 Feb 2.
Background: PubMed 16575267Task Force of the Italian Working Group on Cardiac Rehabilitation Prevention; Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corra U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Apr;13(2):150-64. doi: 10.1097/01.hjr.0000209812.05573.04.
Background: PubMed 16926657Task Force of the Italian Working Group on Cardiac Rehabilitation and Prevention (Gruppo Italiano di Cardiologia Riabilitativa e Prevenzione, GICR); Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology; Piepoli MF, Corra U, Agostoni PG, Belardinelli R, Cohen-Solal A, Hambrecht R, Vanhees L. Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: How to perform cardiopulmonary exercise testing in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2006 Jun;13(3):300-11. doi: 10.1097/00149831-200606000-00003.
Background: PubMed 15394301WEIR JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949 Aug;109(1-2):1-9. doi: 10.1113/jphysiol.1949.sp004363. No abstract available.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Carvedilol and Nebivolol in people with Hypoxia and Altitude, run by Istituto Auxologico Italiano at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Exercise Oxygen Consumption (time frame: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00924833, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2009.