Pulmonary Heart Disease
Conditions
Keywords
Phase 4, DEFINITY®, hemodynamics, pulmonary artery pressure
Brief summary
The purpose of this clinical research is to learn if DEFINITY® 416 will cause any adverse effects during Right Heart Catheterization. This research was requested by the FDA.
Detailed description
This Phase IV safety study will provide safety data on potential systemic and pulmonary hemodynamic effects caused by the administration of DEFINITY® in patients who are to undergo right heart cardiac catheterization for clinical reasons. Using a right heart catheter for direct measurements of pulmonary artery hemodynamics will allow accurate assessments of potential alterations of the pulmonary vasculature. This will be further investigated by the inclusion of two patient populations, one with a baseline pulmonary artery pressure \< 35 mmHg, and one with elevated baseline pulmonary artery pressure. The addition of immune parameter measurements will assess a potential link between systemic and pulmonary alterations and potential immune reactions following DEFINITY® administration. The inclusion of patients in this study is not based on a required echocardiogram with DEFINITY® administration because patients would be exposed to an unjustifiable risk of invasive right heart catheterization and are unlikely to consent to such a procedure. Therefore, patients undergoing heart catheterization for clinical reasons, or patients who are undergoing pulmonary artery hemodynamic assessments will be enrolled and receive DEFINITY® in this study.
Interventions
DRUGDefinity
one bolus dose of Definity per intravenous injection, 30-60 second injection, dose value calculation = maximum of 10 microliter/kg patient weight
Sponsors
Lantheus Medical Imaging
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Appropriate candidate scheduled to undergo right heart catheterization and measurement of pulmonary artery hemodynamics for clinical reasons * Be male or female above the age of 18 * Female patients who no longer have child-bearing potential * Women of Child-Bearing Potential(WOCBP) who: 1. are not pregnant and have been using an adequate and medically approved method of contraception 2. have a negative urine pregnancy test * Be able and willing to communicate effectively with study center personnel.
Exclusion criteria
* Women who are pregnant or lactating * Known hypersensitivity or contraindication to or greater heart block * Previous heart transplant * Known right-to-left shunt (including atrial septal defect) * Severe pulmonary artery hypertension (i.e., \> 75 mmHg * Current uncontrolled ventricular tachycardia * Second-degree or greater heart block * Any contraindications for the use of a right heart catheter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Pulmonary Artery Pressure Change From 1 Minute Pre-dose to 31 - 35 Minutes Post Dose | 31-35 minutes minus baseline | Percent change in pulmonary atery pressure change from immediately pre-dose to 31 - 35 minutes post dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunology Panel- Complement 3A (C3A) | Out to 70 minutes | Evaluate the Immunology Panel after the administration of DEFINITY |
| Immunology Panel- Complement 5A(C5A) | Out to 70 minutes | Evaluate the Immunology Panel after the administration of DEFINITY |
| Immunology Panel- Interleuken-6 | Out to 70 minutes | Evaluate the Immunology Panel after the administration of DEFINITY |
| Immunology Panel- Tryptase | Out to 70 minutes | Evaluate the Immunology Panel after the administration of DEFINITY |
Countries
United States
Participant flow
Recruitment details
participants were recruited from hospitals and clinics in the USA between July 2009 and December 2009
Pre-assignment details
There were no randomization procedures or other pre-assignment requirements in this study.
Participants by arm
| Arm | Count |
|---|---|
| Low Pulmonary Arterial Pressure Subjects with pulmonary arterial pressure (PAP) of \< or = to 35 mmHg. | 16 |
| Elevated Pulmonary Arterial Pressure Subjects with a PAP of \> or = to 35 mmHg. | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Low Pulmonary Arterial Pressure | Elevated Pulmonary Arterial Pressure | Total |
|---|---|---|---|
| Age, Continuous | 56.9 years STANDARD_DEVIATION 10.8 | 57.4 years STANDARD_DEVIATION 15.1 | 57.2 years STANDARD_DEVIATION 12.9 |
| Pulmonary artery pressure 1 minute pre-dose | 30.4 mm Hg STANDARD_DEVIATION 3.38 | 50.9 mm Hg STANDARD_DEVIATION 10.31 | 40.7 mm Hg STANDARD_DEVIATION 12.89 |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 16 | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Percent Change in Pulmonary Artery Pressure Change From 1 Minute Pre-dose to 31 - 35 Minutes Post Dose
Percent change in pulmonary atery pressure change from immediately pre-dose to 31 - 35 minutes post dose
Time frame: 31-35 minutes minus baseline
Population: Per the protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Pulmonary Arterial Pressure | Percent Change in Pulmonary Artery Pressure Change From 1 Minute Pre-dose to 31 - 35 Minutes Post Dose | -1.9 mm Hg | Standard Deviation 18.03 |
| Elevated Pulmonary Arterial Pressure | Percent Change in Pulmonary Artery Pressure Change From 1 Minute Pre-dose to 31 - 35 Minutes Post Dose | -1.7 mm Hg | Standard Deviation 10.25 |
Secondary
Immunology Panel- Complement 3A (C3A)
Evaluate the Immunology Panel after the administration of DEFINITY
Time frame: Out to 70 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Pulmonary Arterial Pressure | Immunology Panel- Complement 3A (C3A) | -45.80 ng/ml | Standard Deviation 338.14 |
| Elevated Pulmonary Arterial Pressure | Immunology Panel- Complement 3A (C3A) | -38.20 ng/ml | Standard Deviation 414.86 |
Secondary
Immunology Panel- Complement 5A(C5A)
Evaluate the Immunology Panel after the administration of DEFINITY
Time frame: Out to 70 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Pulmonary Arterial Pressure | Immunology Panel- Complement 5A(C5A) | -0.95 ng/ml | Standard Deviation 3.56 |
| Elevated Pulmonary Arterial Pressure | Immunology Panel- Complement 5A(C5A) | 0.78 ng/ml | Standard Deviation 4.55 |
Secondary
Immunology Panel- Interleuken-6
Evaluate the Immunology Panel after the administration of DEFINITY
Time frame: Out to 70 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Pulmonary Arterial Pressure | Immunology Panel- Interleuken-6 | 0.31 pg/ml | Standard Deviation 1.46 |
| Elevated Pulmonary Arterial Pressure | Immunology Panel- Interleuken-6 | 0.15 pg/ml | Standard Deviation 2.11 |
Secondary
Immunology Panel- Tryptase
Evaluate the Immunology Panel after the administration of DEFINITY
Time frame: Out to 70 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Pulmonary Arterial Pressure | Immunology Panel- Tryptase | -0.24 ug/ml | Standard Deviation 0.82 |
| Elevated Pulmonary Arterial Pressure | Immunology Panel- Tryptase | -0.01 ug/ml | Standard Deviation 1.46 |