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Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus (PDA:TOLERATE)

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ClinicalTrials.gov Identifier: NCT01958320
Recruitment Status : Completed
First Posted : October 9, 2013
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

October 4, 2013
October 9, 2013
May 4, 2018
December 2013
June 2017   (Final data collection date for primary outcome measure)
The primary outcome will be the 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) [ Time Frame: up to 12 months after hospital discharge ]
Same as current
Complete list of historical versions of study NCT01958320 on ClinicalTrials.gov Archive Site
  • duration of different types of respiratory support (ventilation, CPAP, cannula) [ Time Frame: up to 20 weeks of age ]
  • duration of gavage feeding assistance [ Time Frame: up to 20 weeks of age ]
  • incidence of necrotizing enterocolitis or spontaneous perforation [ Time Frame: up to 20 weeks of age ]
Same as current
Not Provided
Not Provided
 
Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus
Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus in Preterm infants-a Multicenter Trial

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".

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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Early routine, mandated PDA treatment versus Conservative treatment only if Rescue criteria are met
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
  • Patent Ductus Arteriosus
  • Surgery
  • Necrotizing Enterocolitis
  • Intestinal Perforation
  • Other: pharmacologic treatment of the PDA
    Following randomization, infants will be treated with medications used to produce PDA closure.
  • Other: no pharmacologic treatment of the PDA
    Following randomization, infants will NOT be treated with medications used to produce PDA closure (unless they develop rescue criteria at a later point in time).
  • Experimental: Early treatment

    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.

    Intervention: Other: pharmacologic treatment of the PDA
  • Active Comparator: Conservative Treatment

    Infants randomized to the Conservative Treatment approach will receive "no pharmacologic treatment of the PDA" but will be followed to determine if they meet criteria for later PDA "rescue treatment" (Infants will be eligible for rescue treatment of their persistent PDA if they meet the rescue treatment criteria.)

    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.

    Intervention: Other: no pharmacologic treatment of the PDA
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
202
200
June 2017
June 2017   (Final data collection date for primary outcome measure)

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.

    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.

Sexes Eligible for Study: All
up to 14 Days   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Sweden,   Turkey,   United Kingdom,   United States
 
 
NCT01958320
RC4
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
University of California, San Francisco
University of California, San Francisco
Not Provided
Principal Investigator: Ronald Clyman, MD University of California, San Francisco
University of California, San Francisco
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP