Pulmonary Hypertension
Conditions
Keywords
Pulmonary hypertension, Right heart Catheterization
Brief summary
This is an intra-subject crossover comparative safety study to evaluate the effect of intravenous (IV) bolus injection of SonoVue on pulmonary hemodynamics.
Detailed description
Subjects will be divided into two groups based on their baseline mean pulmonary arterial pressure. Each subject will receive two injections in randomized order during right heart catheterization: one administration of SonoVue and one administration of placebo, either SonoVue followed by Placebo or Placebo followed by SonoVue. The purpose is to provide direct evidence on the presence or absence of pulmonary hemodynamic effect following IV administration of SonoVue versus any effects following IV administration of the same volume of placebo.
Interventions
DRUGSonoVue
dose of 4.8 mL administered intravenously one time
DRUGPlacebo
Placebo is normal saline 0.9% for injection used as the comparator administered at 4.8 mL (same dose as SonoVue)
Sponsors
Bracco Diagnostics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provides written informed consent male or female at least 18 years of age scheduled to undergo right heart catheterization for clinical reasons
Exclusion criteria
* Pregnant or lactating females * Significant arrhythmia or non-sinus rhythm that may affect the ability to assess pulmonary hemodynamics by catheterization * Known allergy to one of the ingredients in the investigational product or to any other contrast agents including ultrasound contrast agents * Previously entered into the study or received an investigational compound within 30 days before admission into the study * Unstable pulmonary and/or systemic hemodynamic condition that would affect the ability to evaluate the pharmacological or hemodynamic effect of the investigational products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose) | A total of 36 subjects were enrolled in this crossover study: 18 (8 randomized to placebo then SonoVue and 10 randomized to SonoVue then placebo) in the Hypertension Group (baseline mean pulmonary artery pressure (PAP) \>=25.0 mmHg group) and 18 (10 randomized to placebo then SonoVue and 8 randomized to SonoVue then placebo) in the Normal group (baseline mean PAP \<25.0 mmHg group). All subjects in this study were to have systolic PAP recorded within 5 minutes before the first investigational product administration. This parameter was to be measured and recorded again at 1, 4, 7 and 10 minutes after the administration of each investigational product (SonoVue and Placebo). This outcome measure presents the mean change from baseline in systolic PAP measured in mmHg. Baseline is the average of the 2 measurements within 5 minutes prior to first investigational product administration, therefore, applying to both products. |
| Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose) | All subjects in this study were to have diastolic PAP recorded within 5 minutes before the first investigational product administration. This parameter was to be measured and recorded again at 1, 4, 7 and 10 minutes after the administration of each investigational product (SonoVue and Placebo). This outcome measure presents the mean change from baseline in diastolic PAP measured in mmHg. Baseline is the average of the 2 measurements within 5 minutes prior to first investigational product administration, therefore, applying to both products. |
| Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | Comparison to baseline to 2 post dose timepoints (1 and 10 minutes post dose) | All subjects in this study were to have pulmonary vascular resistance (PVR; measured in dyne x seconds per centimeters to the 5th power) derived from mean PAP (measured in mmHg), pulmonary capillary wedge pressure (PCWP \[mmHg\]) and cardiac output (Qp \[litres per minute\]), each taken 5 minutes prior to the first investigational product administration, calculated using the following formula: \[(mean PAP-PCWP) divided by Qp\] x 80. Baseline is the last measurement prior to first investigational product administration, therefore, applying to both products. Mean PAP, PCWP and Qp were repeated at 1 and 10 minutes post dose; PVR was calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hypertension Group Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥25.0 mmHg) who received SonoVue and Placebo (normal saline 0.9% for injection) in randomized order, both administered intravenously as a single bolus injection of 4.8 mL. | 18 |
| Normal Group Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \<25.0 mmHg) who received SonoVue and Placebo (normal saline 0.9% for injection) in randomized order, both administered intravenously as a single bolus injection of 4.8 mL. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Normal Group | Hypertension Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 6 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 26 Participants |
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.7 | 58.0 years STANDARD_DEVIATION 12.96 | 57.6 years STANDARD_DEVIATION 11.72 |
| Gender Female | 6 Participants | 5 Participants | 11 Participants |
| Gender Male | 12 Participants | 13 Participants | 25 Participants |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline
All subjects in this study were to have diastolic PAP recorded within 5 minutes before the first investigational product administration. This parameter was to be measured and recorded again at 1, 4, 7 and 10 minutes after the administration of each investigational product (SonoVue and Placebo). This outcome measure presents the mean change from baseline in diastolic PAP measured in mmHg. Baseline is the average of the 2 measurements within 5 minutes prior to first investigational product administration, therefore, applying to both products.
Time frame: Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose)
Population: 36 total subjects: 18 subjects (8 assigned to placebo/SonoVue and 10 assigned to SonoVue/placebo) in the Baseline mean PAP \>=25.0 mmHg group (Hypertension Group) and 18 subjects (10 assigned to placebo/SonoVue and 8 assigned to SonoVue/placebo) in the Baseline mean PAP \<25.0 mmHg group (Normal Group).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | -3.22 mmHg | Standard Deviation 5.342 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | -3.39 mmHg | Standard Deviation 4.661 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | -3.44 mmHg | Standard Deviation 5.731 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | -3.56 mmHg | Standard Deviation 4.362 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Diastolic PAP (mmHg) | 24.11 mmHg | Standard Deviation 7.177 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | -2.78 mmHg | Standard Deviation 6.839 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | -3.06 mmHg | Standard Deviation 4.325 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | -1.83 mmHg | Standard Deviation 4.836 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | -1.50 mmHg | Standard Deviation 3.884 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Diastolic PAP (mmHg) | 24.11 mmHg | Standard Deviation 7.177 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | 0.44 mmHg | Standard Deviation 3.508 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Diastolic PAP (mmHg) | 11.72 mmHg | Standard Deviation 3.75 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | 1.44 mmHg | Standard Deviation 3.481 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | 1.61 mmHg | Standard Deviation 2.471 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | 1.39 mmHg | Standard Deviation 2.207 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | 1.09 mmHg | Standard Deviation 3.104 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | 1.22 mmHg | Standard Deviation 4.156 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Diastolic PAP (mmHg) | 11.72 mmHg | Standard Deviation 3.75 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | 0.68 mmHg | Standard Deviation 2.767 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Diastolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | 0.78 mmHg | Standard Deviation 3.723 |
Primary
Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline
All subjects in this study were to have pulmonary vascular resistance (PVR; measured in dyne x seconds per centimeters to the 5th power) derived from mean PAP (measured in mmHg), pulmonary capillary wedge pressure (PCWP \[mmHg\]) and cardiac output (Qp \[litres per minute\]), each taken 5 minutes prior to the first investigational product administration, calculated using the following formula: \[(mean PAP-PCWP) divided by Qp\] x 80. Baseline is the last measurement prior to first investigational product administration, therefore, applying to both products. Mean PAP, PCWP and Qp were repeated at 1 and 10 minutes post dose; PVR was calculated.
Time frame: Comparison to baseline to 2 post dose timepoints (1 and 10 minutes post dose)
Population: 36 total subjects: 18 subjects (8 assigned to placebo/SonoVue and 10 assigned to SonoVue/placebo) in the Baseline mean PAP \>=25.0 mmHg group (Hypertension Group) and 18 subjects (10 assigned to placebo/SonoVue and 8 assigned to SonoVue/placebo) in the Baseline mean PAP \<25.0 mmHg group (Normal Group).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | Baseline PVR (dyne*sec/cm^5) | 307.189 dyne*sec/cm^5 | Standard Deviation 307.6268 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 10 minutes post-dose | -41.468 dyne*sec/cm^5 | Standard Deviation 226.7863 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 1 minute post-dose | -73.087 dyne*sec/cm^5 | Standard Deviation 186.9939 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | Baseline PVR (dyne*sec/cm^5) | 307.189 dyne*sec/cm^5 | Standard Deviation 307.6268 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 10 minutes post-dose | -10.028 dyne*sec/cm^5 | Standard Deviation 175.0397 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 1 minute post-dose | -63.065 dyne*sec/cm^5 | Standard Deviation 158.7097 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 1 minute post-dose | 20.541 dyne*sec/cm^5 | Standard Deviation 63.4305 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | Baseline PVR (dyne*sec/cm^5) | 142.714 dyne*sec/cm^5 | Standard Deviation 93.6055 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 10 minutes post-dose | 21.208 dyne*sec/cm^5 | Standard Deviation 82.9967 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | Baseline PVR (dyne*sec/cm^5) | 142.714 dyne*sec/cm^5 | Standard Deviation 93.6055 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 10 minutes post-dose | -6.117 dyne*sec/cm^5 | Standard Deviation 52.0617 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (Dyne*Sec/cm^5) - Mean Change From Baseline | 1 minute post-dose | 1.021 dyne*sec/cm^5 | Standard Deviation 55.5296 |
Primary
Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline
A total of 36 subjects were enrolled in this crossover study: 18 (8 randomized to placebo then SonoVue and 10 randomized to SonoVue then placebo) in the Hypertension Group (baseline mean pulmonary artery pressure (PAP) \>=25.0 mmHg group) and 18 (10 randomized to placebo then SonoVue and 8 randomized to SonoVue then placebo) in the Normal group (baseline mean PAP \<25.0 mmHg group). All subjects in this study were to have systolic PAP recorded within 5 minutes before the first investigational product administration. This parameter was to be measured and recorded again at 1, 4, 7 and 10 minutes after the administration of each investigational product (SonoVue and Placebo). This outcome measure presents the mean change from baseline in systolic PAP measured in mmHg. Baseline is the average of the 2 measurements within 5 minutes prior to first investigational product administration, therefore, applying to both products.
Time frame: Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose)
Population: 36 total subjects: 18 subjects (8 assigned to placebo/SonoVue and 10 assigned to SonoVue/placebo) in the Baseline mean PAP \>=25.0 mmHg group (Hypertension Group) and 18 subjects (10 assigned to placebo/SonoVue and 8 assigned to SonoVue/placebo) in the Baseline mean PAP \<25.0 mmHg group (Normal Group).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | -1.94 mmHg | Standard Deviation 6.01 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | -2.17 mmHg | Standard Deviation 5.993 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | -2.44 mmHg | Standard Deviation 6.849 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | -3.06 mmHg | Standard Deviation 5.196 |
| Hypertension Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Systolic PAP (mmHg) | 50.50 mmHg | Standard Deviation 17.581 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | -2.94 mmHg | Standard Deviation 5.352 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | -2.28 mmHg | Standard Deviation 4.854 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | -2.17 mmHg | Standard Deviation 5.3 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | -3.33 mmHg | Standard Deviation 5.407 |
| Hypertension SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Systolic PAP (mmHg) | 50.50 mmHg | Standard Deviation 17.581 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | 1.50 mmHg | Standard Deviation 4.345 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Systolic PAP (mmHg) | 30.08 mmHg | Standard Deviation 6.001 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | 1.31 mmHg | Standard Deviation 3.214 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | 0.86 mmHg | Standard Deviation 3.94 |
| Normal Placebo | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | 0.03 mmHg | Standard Deviation 4.816 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 7 minutes post-dose | -0.32 mmHg | Standard Deviation 2.215 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 1 minute post-dose | 0.47 mmHg | Standard Deviation 2.464 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | Baseline Systolic PAP (mmHg) | 30.08 mmHg | Standard Deviation 6.001 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 4 minutes post-dose | 0.62 mmHg | Standard Deviation 2.485 |
| Normal SonoVue | Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Systolic Pulmonary Artery Pressure (mmHg) - Mean Change From Baseline | 10 minutes post-dose | -0.69 mmHg | Standard Deviation 3.945 |