Trial record 1 of 53 for:    "Patent ductus arteriosus"
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Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus (PDA:TOLERATE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01958320
First received: October 4, 2013
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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".


Condition Intervention Phase
Patent Ductus Arteriosus
Surgery
Necrotizing Enterocolitis
Intestinal Perforation
Other: pharmacologic treatment of the PDA
Other: no pharmacologic treatment of the PDA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus in Preterm infants-a Multicenter Trial

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • duration of different types of respiratory support (ventilation, CPAP, cannula) [ Time Frame: up to 20 weeks of age ] [ Designated as safety issue: No ]
  • duration of gavage feeding assistance [ Time Frame: up to 20 weeks of age ] [ Designated as safety issue: No ]
  • incidence of necrotizing enterocolitis or spontaneous perforation [ Time Frame: up to 20 weeks of age ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: December 2013
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Other: pharmacologic treatment of the PDA
Following randomization, infants will be treated with medications used to produce PDA closure.
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.

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).

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.

  Eligibility

Ages Eligible for Study:   up to 14 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

    -

    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.

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01958320

Contacts
Contact: Ronald Clyman, MD 415-476-4462 clymanr@peds.ucsf.edu

Locations
United States, California
Sharp Mary Birch Hospital for Women and Newborns Recruiting
San Diego, California, United States, 92123
Principal Investigator: Anup Katheria, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Ronald Clyman, MD    415-476-4462    clymanr@peds.ucsf.edu   
Principal Investigator: Ronald Clyman, MD         
Kaiser Permanente Santa Clara Recruiting
Santa Clara, California, United States, 95051
Principal Investigator: Andrea Wickremasinghe, MD         
Principal Investigator: Lawrence Dong, MD         
United States, Illinois
Northshore University Health System Recruiting
Evanston, Illinois, United States, 60201
Principal Investigator: Matthew Derrick, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21218
Principal Investigator: Susan Aucott, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55902
Principal Investigator: William Carey, MD         
United States, New Jersey
Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07960
Principal Investigator: Denise Hassinger, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Principal Investigator: Richard Polin, MD         
Principal Investigator: Tina Leone, MD         
United States, Oregon
Providence St Vincent Medical Center Recruiting
Portland, Oregon, United States, 97225
Principal Investigator: Joseph Kaempf, MD         
Turkey
Ankara University School of Medicine Children's Hospital Recruiting
Ankara, Turkey
Principal Investigator: Omer Erdeve, MD         
Sub-Investigator: Dilek kahvecioglu autf, MD         
Sisli Hamidiye Etfal Training and Research Hospital Recruiting
Istanbul, Turkey
Principal Investigator: Ali Bulbul, MD         
Inonu University School of Medicine Turgut Ozal Medical Center Recruiting
Malatya, Turkey
Principal Investigator: Ahmet Karadag, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Ronald Clyman, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01958320     History of Changes
Other Study ID Numbers: RC4
Study First Received: October 4, 2013
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
patent ductus arteriosus
patent ductus arteriosus ligation
necrotizing enterocolitis
spontaneous intestinal perforation

Additional relevant MeSH terms:
Ductus Arteriosus, Patent
Enterocolitis
Intestinal Perforation
Enterocolitis, Necrotizing
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on July 22, 2014