Trial Outcomes & Findings for Safety of SonoVue on Pulmonary Hemodynamics (NCT NCT01306292)

Last Updated: 2016-12-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose)

Results posted on

2016-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Hypertension Group (SonoVue First, Then Placebo) Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who were randomized to receive SonoVue first, then Placebo (normal saline 0.9% for injection). Both agents were administered intravenously as a single bolus injection of 4.8 mL. The two injection were separated by an interval of at least 10 minutes.	Hypertension Group (Placebo First, Then SonoVue) Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥25.0 mmHg) who were randomized to receive Placebo (normal saline 0.9% for injection) first, then SonoVue. Both agents were administered intravenously as a single bolus injection of 4.8 mL. The two injection were separated by an interval of at least 10 minutes.	Normal Group (SonoVue First, Then Placebo) Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \<25.0 mmHg) who were randomized to receive SonoVue first, then Placebo (normal saline 0.9% for injection). Both agents were administered intravenously as a single bolus injection of 4.8 mL. The two injection were separated by an interval of at least 10 minutes.	Normal Group (Placebo First, Then SonoVue) Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \<25.0 mmHg) who were randomized to receive Placebo (normal saline 0.9% for injection) first, then SonoVue. Both agents were administered intravenously as a single bolus injection of 4.8 mL. The two injection were separated by an interval of at least 10 minutes.
First Injection STARTED	10	8	8	10
First Injection COMPLETED	10	8	8	10
First Injection NOT COMPLETED	0	0	0	0
Washout (at Least 10 Minutes) STARTED	10	8	8	10
Washout (at Least 10 Minutes) COMPLETED	10	8	8	10
Washout (at Least 10 Minutes) NOT COMPLETED	0	0	0	0
Second Injection STARTED	10	8	8	10
Second Injection COMPLETED	10	8	7	10
Second Injection NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety of SonoVue on Pulmonary Hemodynamics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hypertension Group n=18 Participants 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.	Normal Group n=18 Participants 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.	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	58.0 years STANDARD_DEVIATION 12.96 • n=5 Participants	57.2 years STANDARD_DEVIATION 10.70 • n=7 Participants	57.6 years STANDARD_DEVIATION 11.72 • n=5 Participants
Gender Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Gender Male	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants	18 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Hypertension Placebo n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Hypertension SonoVue n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.	Normal Placebo n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Normal SonoVue n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.
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 6.010	-2.28 mmHg Standard Deviation 4.854	0.86 mmHg Standard Deviation 3.940	-0.32 mmHg Standard Deviation 2.215
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	50.50 mmHg Standard Deviation 17.581	30.08 mmHg Standard Deviation 6.001	30.08 mmHg Standard Deviation 6.001
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	-3.33 mmHg Standard Deviation 5.407	1.31 mmHg Standard Deviation 3.214	0.47 mmHg Standard Deviation 2.464
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	-2.94 mmHg Standard Deviation 5.352	1.50 mmHg Standard Deviation 4.345	0.62 mmHg Standard Deviation 2.485
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	-2.17 mmHg Standard Deviation 5.300	0.03 mmHg Standard Deviation 4.816	-0.69 mmHg Standard Deviation 3.945

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hypertension Placebo n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Hypertension SonoVue n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.	Normal Placebo n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Normal SonoVue n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.
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	-2.78 mmHg Standard Deviation 6.839	0.44 mmHg Standard Deviation 3.508	0.68 mmHg Standard Deviation 2.767
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	-3.06 mmHg Standard Deviation 4.325	1.61 mmHg Standard Deviation 2.471	1.09 mmHg Standard Deviation 3.104
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	-1.83 mmHg Standard Deviation 4.836	1.39 mmHg Standard Deviation 2.207	0.78 mmHg Standard Deviation 3.723
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	24.11 mmHg Standard Deviation 7.177	11.72 mmHg Standard Deviation 3.750	11.72 mmHg Standard Deviation 3.750
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	-1.50 mmHg Standard Deviation 3.884	1.44 mmHg Standard Deviation 3.481	1.22 mmHg Standard Deviation 4.156

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hypertension Placebo n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Hypertension SonoVue n=18 Participants Subjects with pulmonary hypertension (baseline mean pulmonary arterial pressure ≥ 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.	Normal Placebo n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received Placebo (normal saline 0.9%) administered intravenously as a single bolus injection of 4.8 mL.	Normal SonoVue n=18 Participants Subjects without pulmonary hypertension (baseline mean pulmonary arterial pressure \< 25.0 mmHg) who received SonoVue administered intravenously as a single bolus injection of 4.8 mL.
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	-63.065 dyne*sec/cm^5 Standard Deviation 158.7097	20.541 dyne*sec/cm^5 Standard Deviation 63.4305	1.021 dyne*sec/cm^5 Standard Deviation 55.5296
Effects of SonoVue and Placebo on Pulmonary Hemodynamics: Pulmonary Vascular Resistance (DyneSec/cm^5) - Mean Change From Baseline Baseline PVR (dynesec/cm^5)	307.189 dyne*sec/cm^5 Standard Deviation 307.6268	307.189 dyne*sec/cm^5 Standard Deviation 307.6268	142.714 dyne*sec/cm^5 Standard Deviation 93.6055	142.714 dyne*sec/cm^5 Standard Deviation 93.6055
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	-10.028 dyne*sec/cm^5 Standard Deviation 175.0397	21.208 dyne*sec/cm^5 Standard Deviation 82.9967	-6.117 dyne*sec/cm^5 Standard Deviation 52.0617

Adverse Events

Hypertension Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Normal Pulmonary Pressure Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Hypertension Group n=18 participants at risk 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. An interval of at least 10 minutes was allowed between the two injections (SonoVue and Placebo). All adverse events occurred hours after the completion of both injections and for the purposes of this study have been assigned to the administration of SonoVue.	Normal Pulmonary Pressure Group n=18 participants at risk 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. An interval of at least 10 minutes was allowed between the two injections (SonoVue and Placebo). All adverse events occurred hours after the completion of both injections and for the purposes of this study have been assigned to the administration of SonoVue.
General disorders Catheter site pain	5.6% 1/18 • Number of events 1 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.	0.00% 0/18 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.
General disorders Chills	0.00% 0/18 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.	5.6% 1/18 • Number of events 1 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/18 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.	5.6% 1/18 • Number of events 1 • Adverse events were to be monitored from the time of signed informed consent until 24 hours after the last investigational product administration.

Additional Information

Dr. Maria Luigia Storto

Bracco Diagnostics Inc.

Phone: 609-514-2262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60