Inhaled Prostaglandin E1 (IPGE1) for Hypoxemic Respiratory Failure (NHRF)
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ClinicalTrials.gov Identifier: NCT01467076 |
Recruitment Status
:
Terminated
(The study was halted due to futility concerns based on the unmet benchmarks as specified in the pilot study protocol.)
First Posted
: November 8, 2011
Results First Posted
: December 30, 2016
Last Update Posted
: December 30, 2016
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Sponsor:
NICHD Neonatal Research Network
Collaborators:
National Center for Research Resources (NCRR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
NICHD Neonatal Research Network
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First Submitted Date ICMJE | October 17, 2011 | ||||||||||||||||||||||||||||||||||||
First Posted Date ICMJE | November 8, 2011 | ||||||||||||||||||||||||||||||||||||
Results First Submitted Date | November 3, 2016 | ||||||||||||||||||||||||||||||||||||
Results First Posted Date | December 30, 2016 | ||||||||||||||||||||||||||||||||||||
Last Update Posted Date | December 30, 2016 | ||||||||||||||||||||||||||||||||||||
Study Start Date ICMJE | November 2011 | ||||||||||||||||||||||||||||||||||||
Actual Primary Completion Date | May 2012 (Final data collection date for primary outcome measure) | ||||||||||||||||||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
Assess Feasibility to Recruit at Least 50 Infants [ Time Frame: 9 months after 75% of the participating sites are enrolling ] The primary outcome is the ability to recruit adequate number of infants (n=50) in a 9 month period without excessive (>20%) protocol violations.
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Original Primary Outcome Measures ICMJE |
Assess Feasibility [ Time Frame: 9 months after 75% of the participating sites are enrolling ] The primary outcome is the ability to recruit adequate number of patients (50) in a 9 month period without excessive (>20%) protocol violations
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Change History | Complete list of historical versions of study NCT01467076 on ClinicalTrials.gov Archive Site | ||||||||||||||||||||||||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Outcome Measures ICMJE | Not Provided | ||||||||||||||||||||||||||||||||||||
Original Other Outcome Measures ICMJE | Not Provided | ||||||||||||||||||||||||||||||||||||
Descriptive Information | |||||||||||||||||||||||||||||||||||||
Brief Title ICMJE | Inhaled Prostaglandin E1 (IPGE1) for Hypoxemic Respiratory Failure (NHRF) | ||||||||||||||||||||||||||||||||||||
Official Title ICMJE | Pilot Randomized Clinical Trial of Inhaled PGE1 in Neonates With Sub-Optimal Response to Inhaled Nitric Oxide | ||||||||||||||||||||||||||||||||||||
Brief Summary | This is a randomized controlled trial (RCT) on the use of Inhaled prostaglandin E1 (IPGE1) in Neonatal Hypoxemic Respiratory Failure (NHRF). Fifty patients recruited at 10 high volume sites within the NICHD Neonatal Research Network will constitute a pilot sample to evaluate the feasibility and safety of prolonged IPGE1 administration and determination of optimal dose. In this Pilot RCT, two doses of IPGE1 (300 and 150 ng/kg/min) will be administered over a maximum duration of 72 hours and compared with placebo. Once feasibility and safety of IPGE1 administered over 72 hours has been demonstrated in the pilot trial, a full scale randomized controlled trial will be planned. | ||||||||||||||||||||||||||||||||||||
Detailed Description | Hypoxemic respiratory failure in the newborn (NHRF) is usually associated with widespread vasoconstriction of the pulmonary microvasculature giving rise to intra- and extra-pulmonary shunts and profound hypoxemia. The goal of therapy is to decrease the regional pulmonary vascular resistance of ventilated lung areas thus decreasing intrapulmonary shunting and selectively reducing the pulmonary-artery pressure without causing systemic vasodilation. Intravenously administered vasodilators lack pulmonary selectivity leading to systemic side effects. Inhaled nitric oxide (INO), a selective pulmonary vasodilator, has revolutionized the treatment of respiratory failure in the newborn. However, there is lack of sustained improvement in 30-46% of infants; moreover, INO requires specialized systems for administration, making the treatment expensive. Aerosolized prostaglandins I2 and E1 have been reported to be effective selective pulmonary vasodilators in animals and human adults. In addition, inhaled prostaglandin I2 (IPGI2) has also been reported to be effective in preterm and term newborns, and children with pulmonary hypertension. Although intravenous PGE1 is widely used in neonates, the use of the inhaled form has not been reported in newborns with pulmonary hypertension. Compared to PGI2, PGE1 has a shorter half-life, lower acidity constant (pKa) (6.3 versus 10.5), bronchodilator action, anti-proliferative and anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung. Prostaglandin nebulization can be used without the sophisticated technical equipment needed for controlled NO inhalation and hence is less expensive. It has no known toxic metabolites or toxic effects. Prostaglandins and nitric oxide (NO) relax the vascular smooth muscles through two different second-messenger systems; therefore, in combination, INO and IPGE1 may have synergistic effect. The existing literature suggests that inhaled PGE1 is a potential effective vasodilator in the treatment of NHRF . We have reported the safety and feasibility of short-term administration of inhaled PGE1 in an un-blinded Phase I/II dose-escalation study. Four doses ranging from 25 to 300 ng/kg/min were tested for a maximum duration of 3 hours. We have also reported the stability of IPGE1, its emitted dose and aerosol particle size distribution (APSD) in a neonatal ventilator circuit. In addition we have demonstrated the safety of high dose IPGE1 (1200 ng/kg/min) over 24 hours in ventilated piglets. In the current protocol, we propose a pilot to evaluate the feasibility and safety of prolonged IPGE1 in NHRF. Two doses of IPGE1 (300 and 150 ng/kg/min) will be tested followed by weaning for a maximum duration of 72 hours to determine feasibility, safety, optimal dose and duration of therapy in 50 patients in ten NICHD NRN sites. An IND status has been approved by the FDA for this trial. | ||||||||||||||||||||||||||||||||||||
Study Type ICMJE | Interventional | ||||||||||||||||||||||||||||||||||||
Study Phase | Phase 2 | ||||||||||||||||||||||||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Factorial Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms |
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Publications * | Sood BG, Keszler M, Garg M, Klein JM, Ohls R, Ambalavanan N, Cotten CM, Malian M, Sanchez PJ, Lakshminrusimha S, Nelin LD, Van Meurs KP, Bara R, Saha S, Das A, Wallace D, Higgins RD, Shankaran S; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Inhaled PGE1 in neonates with hypoxemic respiratory failure: two pilot feasibility randomized clinical trials. Trials. 2014 Dec 12;15:486. doi: 10.1186/1745-6215-15-486. | ||||||||||||||||||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||||||||||||||||||||||
Recruitment Status ICMJE | Terminated | ||||||||||||||||||||||||||||||||||||
Actual Enrollment ICMJE |
7 | ||||||||||||||||||||||||||||||||||||
Original Estimated Enrollment ICMJE |
50 | ||||||||||||||||||||||||||||||||||||
Actual Study Completion Date | June 2012 | ||||||||||||||||||||||||||||||||||||
Actual Primary Completion Date | May 2012 (Final data collection date for primary outcome measure) | ||||||||||||||||||||||||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | up to 7 Days (Child) | ||||||||||||||||||||||||||||||||||||
Accepts Healthy Volunteers | No | ||||||||||||||||||||||||||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||||||||||||||||||||||||||
Listed Location Countries ICMJE | United States | ||||||||||||||||||||||||||||||||||||
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Administrative Information | |||||||||||||||||||||||||||||||||||||
NCT Number ICMJE | NCT01467076 | ||||||||||||||||||||||||||||||||||||
Other Study ID Numbers ICMJE | NICHD-NRN-0046 U10HD040689 ( U.S. NIH Grant/Contract ) U10HD021385 ( U.S. NIH Grant/Contract ) U10HD027904 ( U.S. NIH Grant/Contract ) U10HD027880 ( U.S. NIH Grant/Contract ) U10HD034216 ( U.S. NIH Grant/Contract ) U10HD040492 ( U.S. NIH Grant/Contract ) U10HD053109 ( U.S. NIH Grant/Contract ) U10HD040461 ( U.S. NIH Grant/Contract ) U10HD068263 ( U.S. NIH Grant/Contract ) U10HD068270 ( U.S. NIH Grant/Contract ) U10HD068278 ( U.S. NIH Grant/Contract ) U10HD036790 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||||||||||||||||||||||||||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||||||||||||||||||||||||||||||
IPD Sharing Statement | Not Provided | ||||||||||||||||||||||||||||||||||||
Responsible Party | NICHD Neonatal Research Network | ||||||||||||||||||||||||||||||||||||
Study Sponsor ICMJE | NICHD Neonatal Research Network | ||||||||||||||||||||||||||||||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | NICHD Neonatal Research Network | ||||||||||||||||||||||||||||||||||||
Verification Date | November 2016 | ||||||||||||||||||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |