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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01HL102235 | U.S. NIH Grant/Contract | View source |
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This trial was terminated early due to lack of recruitment.
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| State University of New York at Buffalo | OTHER |
| Vanderbilt University | OTHER |
| Ann & Robert H Lurie Children's Hospital of Chicago |
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The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension.
Term infants with respiratory failure and persistent pulmonary hypertension (PPHN) are among the most critically ill infants in the NICU, with significant mortality and morbidity reported even for infants with moderate disease. Currently, management is largely supportive, and includes oxygen, mechanical ventilation (conventional or high frequency ventilation), and exogenous surfactant therapy. Inhaled nitric oxide (iNO) is a pulmonary vasodilator that was approved for the treatment of hypoxic respiratory failure (HRF) and PPHN of the newborn in 1999 based on clinical trials showing a reduction in the need for rescue treatment with extracorporeal membrane oxygenation (ECMO).
One promising therapy to decrease pulmonary arterial pressure and improve oxygenation is sildenafil. Sildenafil is a cGMP-specific phosphodiesterase inhibitor that causes relatively selective pulmonary vasodilation. The use of intravenous (IV) sildenafil was recently FDA approved for use in adults in PPHN. A pilot trial studying dose response and pharmacokinetics in 36 term newborns with PPHN found that IV sildenafil was well tolerated and has the potential to induce marked improvements in oxygenation. The data from this pilot trial provided background to support the dosing regimen for this Phase II trial. We hypothesize that IV sildenafil will acutely reduce pulmonary artery pressure and improve oxygenation in near-term and term infants with PPHN, thus reducing the need for rescue therapy iNO and/or ECMO.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous Sildenafil | Experimental |
| |
| Placebo | Placebo Comparator | 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous Sildenafil | Drug | 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement in Oxygenation | From baseline values at 4 and 24 hours | |
| Receipt of Standard Therapy at Any Point During the 7-day Treatment Period | Receipt of standard therapy (inhaled nitric oxide [iNO] and/or extracorporeal membrane oxygenation [ECMO]) at any point during the 7-day treatment period | 7-day treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Pulmonary Arterial Pressure | Change in pulmonary arterial pressure as calculated by echocardiography | Baseline and 4 hours post study drug administration |
| Duration of Supplemental O2 |
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Inclusion Criteria:
Signed informed consent from legally acceptable guardian
PPHN or hypoxemic respiratory failure associated with:
Greater than or equal to 35 weeks gestation
Age at enrollment less than 72 hours
Moderate hypoxemic respiratory failure, with 12\
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| Name | Affiliation | Role |
|---|---|---|
| John Kinsella, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Health Sciences Center | Aurora | Colorado | 80045 | United States | ||
| Northwestern Memorial Hospital |
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This trial was terminated early due to lack of recruitment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intravenous Sildenafil | Intravenous Sildenafil: 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| OTHER |
| University of Utah | OTHER |
| University of Alabama at Birmingham | OTHER |
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|
| Placebo | Other | An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
|
| Participants will be on supplemental O2 an average of 2 weeks |
| Age at Hospital Discharge | Participants will be followed for the duration of hospital stay, an expected average of 3 weeks |
| Duration of Mechanical Ventilation | Participants will be on mechanical ventilation an average of 1 week |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Anne and Robert H Lurie Children's Hospital of Chicago | Chicago | Illinois | 60614 | United States |
| Women's & Children's Hospital of Buffalo SUNY | Buffalo | New York | 14222 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| Primary Children's Medical Center, Utah | Salt Lake City | Utah | 84113 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. Placebo: An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Newborns meeting entry criteria
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| ID | Title | Description |
|---|---|---|
| BG000 | Intravenous Sildenafil | Intravenous Sildenafil: 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
| BG001 | Placebo | 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. Placebo: An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Age of Newborns in days | Number | participants |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Improvement in Oxygenation | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | From baseline values at 4 and 24 hours |
|
| |||||||||||||||||||||||
| Primary | Receipt of Standard Therapy at Any Point During the 7-day Treatment Period | Receipt of standard therapy (inhaled nitric oxide [iNO] and/or extracorporeal membrane oxygenation [ECMO]) at any point during the 7-day treatment period | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | 7-day treatment period |
|
| ||||||||||||||||||||||
| Secondary | Change in Pulmonary Arterial Pressure | Change in pulmonary arterial pressure as calculated by echocardiography | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | Baseline and 4 hours post study drug administration |
|
| ||||||||||||||||||||||
| Secondary | Duration of Supplemental O2 | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | Participants will be on supplemental O2 an average of 2 weeks |
|
| |||||||||||||||||||||||
| Secondary | Age at Hospital Discharge | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | Participants will be followed for the duration of hospital stay, an expected average of 3 weeks |
|
| |||||||||||||||||||||||
| Secondary | Duration of Mechanical Ventilation | This trial was terminated early due to lack of recruitment. No participants completed the study. Data required to assess this outcome measure was not collected. | Posted | Participants will be on mechanical ventilation an average of 1 week |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intravenous Sildenafil | Intravenous Sildenafil: 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG001 | Placebo | 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. Placebo: An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. | 0 | 2 | 1 | 2 | 0 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PaO2 < 40 | Respiratory, thoracic and mediastinal disorders |
|
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Given that this trial was stopped with only 3 patients randomized, the results are little more than anecdote except that the participants were randomized.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Kinsella, MD | University of Colorado, Denver | 303-724-2853 | John.Kinsella@ucdenver.edu |
| ID | Term |
|---|---|
| D012131 | Respiratory Insufficiency |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Participants |
|