Safety of SonoVue on Pulmonary Hemodynamics

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: SonoVue
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary hypertension, Right heart Catheterization