Safety of SonoVue on Pulmonary Hemodynamics

A Phase II, Double-Blind, Randomized, Placebo-Controlled, Crossover, Safety Study of the Effect of Intravenous Bolus Injections of SonoVue on Pulmonary Hemodynamics in Subjects With and Without Pulmonary Hypertension

This is an intra-subject crossover comparative safety study to evaluate the effect of intravenous (IV) bolus injection of SonoVue on pulmonary hemodynamics.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: SonoVue; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SonoVue; Ultrasound contrast agent under development	Drug: SonoVue; dose of 4.8 mL administered intravenously one time; Other Names: sulfur hexafluoride lipid-type A microspheres; sulfur hexafluoride microbubbles
PLACEBO_COMPARATOR: Placebo; normal saline 0.9% for injection used as the comparator	Drug: Placebo; Placebo is normal saline 0.9% for injection used as the comparator administered at 4.8 mL (same dose as SonoVue); Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose)
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.	Comparison to baseline to 4 post dose timepoints (1, 4, 7 and 10 minutes post dose)
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.	Comparison to baseline to 2 post dose timepoints (1 and 10 minutes post dose)

Collaborators and Investigators

• Sponsor: Bracco Diagnostics, Inc

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (ESTIMATE): March 1, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 7, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Right heart Catheterization
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: BR1-133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study of Lumason pulmonary hemodynamics