Brief Title
Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus
Official Title
Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus in Preterm infants-a Multicenter Trial
Brief Summary
The primary goal of the trial is to compare two different Patent Ductus Arteriosus (PDA)
treatment approaches: 1) an "early treatment" approach or 2) a "conservative" approach. For
the purposes of the study infants will be enrolled if they are delivered before 28 weeks
gestation and have a moderate/large PDA present at 5-7 days after birth.
The hypothesis is: treatment of a moderate size patent ductus arteriosus (PDA) will decrease
the time needed for assisted respiratory support, diuretic therapy, and gavage feeding
assistance, in addition to decreasing the incidence of ductus ligations or need for future
outpatient cardiology follow-up appointments. The investigators hypothesize that one or more
of these benefits will occur without an increase in the time taken to achieve full enteral
feedings or in the incidence of necrotizing enterocolitis (NEC) or spontaneous intestinal
perforations (SIP).The investigators will be comparing the effectiveness of early
pharmacologic treatment with a control group of conservatively managed infants who will only
receive treatment if they meet specific criteria for "rescue treatment".
Detailed Description
Prior studies showed that, if a moderate/large Patent Ductus Arteriosus (PDA) is still
present at 5 days after birth (among infants delivered at 23 and 0/7 to 25 and 6/7 weeks
gestation) or at 7 days after birth (among infants delivered at 26 and 0/7 to 27 and 6/7
weeks gestation), it will persist for at least another 4-12 weeks if it is left untreated.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Infants Who Undergo in Hospital PDA Ligations or Who Have an Open Ductus at the Time of Discharge (That Need Future Outpatient Cardiology Follow-up Visits)
Secondary Outcome
Duration of Gavage Feeding Assistance
Condition
Patent Ductus Arteriosus
Intervention
pharmacologic treatment of the PDA
Study Arms / Comparison Groups
Early treatment
Description: Infants randomized to the early treatment group will receive "pharmacologic treatment of the PDA" to produce PDA closure. Within 24-36 hr following the last treatment dose an echocardiogram will be obtained to document the degree of ductus closure or patency. Echocardiograms will be obtained at 1) 10-14 days after study entry (if the PDA was open and of moderate size on the last echocardiogram), and 2) at the time of hospital discharge (if the PDA was open (any size) on the last echocardiogram). The echocardiogram obtained at discharge will be used to determine the need for outpatient follow-up.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
202
Start Date
December 2013
Completion Date
June 2017
Primary Completion Date
June 2017
Eligibility Criteria
Inclusion Criteria:
This will be a prospective randomized, multi-center, controlled trial that will enroll
infants delivered between 23 & 0/7 - 27 & 6/7 weeks gestation:
1. infants must be between 5-14 days old (if delivered between 23 and 0/7 - 25 and 6/7
weeks) or 7-14 days old (if delivered between 26 & 0/7 - 27 & 6/7 weeks) and
2. have a "moderate size PDA" (defined as a PDA on echocardiogram that has at least one
of the following criteria: internal ductus diameter ≥1.5 mm/kg (or PDA:LPA ratio
≥0.5), ductus flow velocity ≤2.5 m/s or mean pressure gradient across the ductus <8
mm, LA/Ao ratio ≥1.5, left pulmonary artery diastolic (or mean) flow velocity >0.2 (or
>0.42) m/sec, respectively, and/or reversed diastolic flow in the descending
aorta)(13, 68, 69) and
3. are receiving respiratory support consisting of either mechanical ventilation, nasal
CPAP, SiPAP, or nasal cannula flow ≥2 L/min.
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Exclusion Criteria:
prior treatment with indomethacin, ibuprofen, or acetaminophen, contraindications for
the use of indomethacin, ibuprofen, or acetaminophen (these include: hydrocortisone
administration within 24 hrs, urine output < 1 ml/kg/h during the preceding 8 h, serum
creatinine level >1.6 mg/dl, platelet count <50, 000/mm3, abnormal coagulation
studies, or total bilirubin concentration (in mg/dL) > 8 x weight (in kg)),
chromosomal anomalies, congenital or acquired gastrointestinal anomalies, prior
episode of necrotizing enterocolitis or intestinal perforation.
-
Gender
All
Ages
N/A - 14 Days
Accepts Healthy Volunteers
No
Contacts
Ronald Clyman, MD, ,
Location Countries
Sweden
Location Countries
Sweden
Administrative Informations
NCT ID
NCT01958320
Organization ID
RC4
Responsible Party
Sponsor
Study Sponsor
University of California, San Francisco
Study Sponsor
Ronald Clyman, MD, Principal Investigator, University of California, San Francisco
Verification Date
November 2018