Ignite Creation Date:
2024-05-05 @ 7:56 PM
Last Modification Date:
2024-10-26 @ 9:56 AM
Study NCT ID:
NCT00772135
Status:
UNKNOWN
Last Update Posted:
2008-10-15
First Post:
2008-10-14
Brief Title:
Reversibility by Sildenafil of Exercise-Induced Abnormal Right Ventricular Pressure Response in ASD and VSD-Operated Patients
Sponsor:
Oslo University Hospital
Organization:
Oslo University Hospital
Study Overview
Official Title:
Pulmonary Hypertension in Adolescents and Adults With Congenital Heart Disease
Status:
UNKNOWN
Status Verified Date:
2008-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether oral sildenafil citrate reduces the abnormal right ventricular pressure response during exercise in adolescent and adult patients with specific types of congenital heart defects
Detailed Description:
133 Study design and protocol
1331 Design double-blind case-control cross-over study
1332 Patients inclusion exclusion criteria
The study consists of 12-16 patients from the main study see main protocol who are selected by following criteria
Abnormal right ventricular pressure response to exercise cut-off 45 mmHg maximal RVSP during exercise
Informed consent to participation including use of sildenafil placebo The patients will be approximately one year older than during the initial study
1333 Examination protocol
The patients will be examined similarly twice with at least 12 hours and one night sleep between these activities to ensure drug washout One hour before each study part a pharmacy produced capsule envelope coded and drawn in a random manner from a box containing either sildenafil citrate 50 mg or placebo will be administered In this manner each patient will be tested once with placebo use and once with sildenafil use respectively
The participant is taken to a clinical exercise physiology laboratory for testing separated by a nights sleep and at least 12 hours
Monitoring equipment is mounted during the period of drug absorbtion and distribution
1 One minute handgrip static exercise is performed as described with 80 of maximal strength applied BP response is registered beat to beat
2 Pulmonary function is examined including pulmonary volumes single breath technical description see below and spirometry
3 Cardiopulmonary exercise testing according to main protocol see 38
4 Exercise echocardiography during supine bicycle exercise is performed as described in main protocol see 37 Other monitoring during supine cycle exercise
1 ECG
2 Diffusion capacity is monitored intra breath technical description below For equipment calibration haemoglobin concentration is measured by fingertip blood sampling before and after cycle exercise
3 Cardiac output and peripheral oxygen saturation is continuously monitored by Task Force Monitor see below
5 Pulmonary function testing is repeated
6 Handgrip testing is repeated as in 1
Difffusion capacity monitoring There are two ways of measuring diffusion capacity using SensorMedics V-max analyzing system Yorba Linda CA USA - intra breath and single breath
Measurements of forced vital capacity FVC forced expiratory volume FEV1 FEV1 ratio FEV1FVC peak expiratory flow PEF total lung capacity TLC or VA diffusion capacity for carbon monoxide TLCO adjusted diffusing capacity TLCOVA residual volume RV capillary blood volume Vc and membrane conductance Dm are included in the analysis and will be performed according to European Respiratory Society standards
Single breath The diffusion capacity is used to estimate the amount of gas travelling from lungs to the bloodstream across the membrane In the process methane CH4 is used in the concentration of 03 03 carbon monoxide CO 21 oxygen O2 and nitrogen N2 In the estimation of TLCO several measurements are included 1 the area of gas transportation between alveoli and the capillaries A 2 the wall thickness membrane between the alveoli and the erythrocytes T 3 the amount of haemoglobin available Hb and 4 the reaction rate of CO too Hb θ are determinants for the amount of CO that manage to diffuse across to the blood57
In the process CH4 is used as a marker as it does not diffuse across to the blood but become diluted CH4 mixes with the residual volume in the lungs and the degree of dilution is used to calculate alveoli volume CO diffuses across to the blood in addition to become diluted By measuring the amount of CO and CH4 in the expiration air compared to the inhaled gas after a hold of breath in 8-10 seconds we get an expression for the diffusion capacity in the lungs
Figure 1 The single-breath method for TLCO Intra breath Intra breath reefers to the continuous real-time measurement of carbon monoxide uptake by the pulmonary capillary blood during a single breath maneuver Intra breath maneuver may be performed during exercise
The calibration procedure samples to set the span points to 03 CO and 03 CH4 methane The patient starts with normal breathing and is then instructed to exhale as much as possible - then inhale completely After total inhalation the patient should exhale at a slow even flow until the computer end the test The test window shows gas concentration versus time and volume versus time tracing in real time during the maneuver The flow versus time curve is shown simultaneously The collection interval used in the calculation of the TLCO is extending from 20 - 80 of the exhaled volume marked area in figure 2
Figure 2 The intra breath method for TLCO
The patients need to practice this maneuver at rest before using it during exercise The exhalation time is reduced during exercise but the patients must try to exhale as slowly as they can in order for the analysis to be correct
Cardiopulmonary monitoring and analysis When analysing changes in vascular resistances during exercise a measurement of pressure is only a part of the hemodynamic picture According to Ohms law blood flow measurement is necessary to conclude about the vascular resistances For this purpose a non-invasive cardiac stroke volume analyser based on thoracic impedance technique will be usedTask Force Monitor CNS systems product description enclosed This equipment is validated for cardiac output monitoring as compared with thermodilution as gold standard Combined with a beat to beat finger cuff system for measurement of blood pressure this machine produces core circulatory parameters continuously Autonomic nervous function BP variation HR variation and baroreflex sensitivity is also analysed
Continuous measurement of peripheral oxygen saturation is registered with Masimo SET pulse oximeters
134 Statistics
Responses with and without sildenafil will be compared within same individual For parameters affected by calibration differences in machinery from test 1 to 2 delta values will be compared
Power analysis
Data from the main study allow estimations of anticipated results and statistical power If the average of maximal RVSP during exercise in our group is 50 mmHg and sildenafil causes a 20 decrease in average to 40 mmHg SD 100 a sample size of 13 patients leads to statistical power of 817 with 5 confidence level calculation DSS research 1072008 httpwwwdssresearchcomtoolkitspcalcpower_a2asp
1331 Design double-blind case-control cross-over study
1332 Patients inclusion exclusion criteria
The study consists of 12-16 patients from the main study see main protocol who are selected by following criteria
Abnormal right ventricular pressure response to exercise cut-off 45 mmHg maximal RVSP during exercise
Informed consent to participation including use of sildenafil placebo The patients will be approximately one year older than during the initial study
1333 Examination protocol
The patients will be examined similarly twice with at least 12 hours and one night sleep between these activities to ensure drug washout One hour before each study part a pharmacy produced capsule envelope coded and drawn in a random manner from a box containing either sildenafil citrate 50 mg or placebo will be administered In this manner each patient will be tested once with placebo use and once with sildenafil use respectively
The participant is taken to a clinical exercise physiology laboratory for testing separated by a nights sleep and at least 12 hours
Monitoring equipment is mounted during the period of drug absorbtion and distribution
1 One minute handgrip static exercise is performed as described with 80 of maximal strength applied BP response is registered beat to beat
2 Pulmonary function is examined including pulmonary volumes single breath technical description see below and spirometry
3 Cardiopulmonary exercise testing according to main protocol see 38
4 Exercise echocardiography during supine bicycle exercise is performed as described in main protocol see 37 Other monitoring during supine cycle exercise
1 ECG
2 Diffusion capacity is monitored intra breath technical description below For equipment calibration haemoglobin concentration is measured by fingertip blood sampling before and after cycle exercise
3 Cardiac output and peripheral oxygen saturation is continuously monitored by Task Force Monitor see below
5 Pulmonary function testing is repeated
6 Handgrip testing is repeated as in 1
Difffusion capacity monitoring There are two ways of measuring diffusion capacity using SensorMedics V-max analyzing system Yorba Linda CA USA - intra breath and single breath
Measurements of forced vital capacity FVC forced expiratory volume FEV1 FEV1 ratio FEV1FVC peak expiratory flow PEF total lung capacity TLC or VA diffusion capacity for carbon monoxide TLCO adjusted diffusing capacity TLCOVA residual volume RV capillary blood volume Vc and membrane conductance Dm are included in the analysis and will be performed according to European Respiratory Society standards
Single breath The diffusion capacity is used to estimate the amount of gas travelling from lungs to the bloodstream across the membrane In the process methane CH4 is used in the concentration of 03 03 carbon monoxide CO 21 oxygen O2 and nitrogen N2 In the estimation of TLCO several measurements are included 1 the area of gas transportation between alveoli and the capillaries A 2 the wall thickness membrane between the alveoli and the erythrocytes T 3 the amount of haemoglobin available Hb and 4 the reaction rate of CO too Hb θ are determinants for the amount of CO that manage to diffuse across to the blood57
In the process CH4 is used as a marker as it does not diffuse across to the blood but become diluted CH4 mixes with the residual volume in the lungs and the degree of dilution is used to calculate alveoli volume CO diffuses across to the blood in addition to become diluted By measuring the amount of CO and CH4 in the expiration air compared to the inhaled gas after a hold of breath in 8-10 seconds we get an expression for the diffusion capacity in the lungs
Figure 1 The single-breath method for TLCO Intra breath Intra breath reefers to the continuous real-time measurement of carbon monoxide uptake by the pulmonary capillary blood during a single breath maneuver Intra breath maneuver may be performed during exercise
The calibration procedure samples to set the span points to 03 CO and 03 CH4 methane The patient starts with normal breathing and is then instructed to exhale as much as possible - then inhale completely After total inhalation the patient should exhale at a slow even flow until the computer end the test The test window shows gas concentration versus time and volume versus time tracing in real time during the maneuver The flow versus time curve is shown simultaneously The collection interval used in the calculation of the TLCO is extending from 20 - 80 of the exhaled volume marked area in figure 2
Figure 2 The intra breath method for TLCO
The patients need to practice this maneuver at rest before using it during exercise The exhalation time is reduced during exercise but the patients must try to exhale as slowly as they can in order for the analysis to be correct
Cardiopulmonary monitoring and analysis When analysing changes in vascular resistances during exercise a measurement of pressure is only a part of the hemodynamic picture According to Ohms law blood flow measurement is necessary to conclude about the vascular resistances For this purpose a non-invasive cardiac stroke volume analyser based on thoracic impedance technique will be usedTask Force Monitor CNS systems product description enclosed This equipment is validated for cardiac output monitoring as compared with thermodilution as gold standard Combined with a beat to beat finger cuff system for measurement of blood pressure this machine produces core circulatory parameters continuously Autonomic nervous function BP variation HR variation and baroreflex sensitivity is also analysed
Continuous measurement of peripheral oxygen saturation is registered with Masimo SET pulse oximeters
134 Statistics
Responses with and without sildenafil will be compared within same individual For parameters affected by calibration differences in machinery from test 1 to 2 delta values will be compared
Power analysis
Data from the main study allow estimations of anticipated results and statistical power If the average of maximal RVSP during exercise in our group is 50 mmHg and sildenafil causes a 20 decrease in average to 40 mmHg SD 100 a sample size of 13 patients leads to statistical power of 817 with 5 confidence level calculation DSS research 1072008 httpwwwdssresearchcomtoolkitspcalcpower_a2asp
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2006 2 0012 | None | None | None |