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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
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Conditions Patent Ductus Arteriosus
Surgery
Necrotizing Enterocolitis
Intestinal Perforation
Interventions Other: pharmacologic treatment of the PDA
Other: no pharmacologic treatment of the PDA
Drug: NSAID
Enrollment 202
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Period Title: Overall Study
Started 104 98
Completed 104 98
Not Completed 0 0
Arm/Group Title Early Treatment Conservative Treatment Total
Hide Arm/Group 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.

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

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.

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).

Total of all reporting groups
Overall Number of Baseline Participants 104 98 202
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 98 participants 202 participants
<=18 years
104
 100.0%
98
 100.0%
202
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Days after birth
Number Analyzed 104 participants 98 participants 202 participants
8.1  (2.1) 8.3  (2.3) 8.2  (2.2)
[1]
Measure Description: days after birth
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 98 participants 202 participants
Female
56
  53.8%
55
  56.1%
111
  55.0%
Male
48
  46.2%
43
  43.9%
91
  45.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 98 participants 202 participants
Hispanic or Latino
25
  24.0%
19
  19.4%
44
  21.8%
Not Hispanic or Latino
79
  76.0%
79
  80.6%
158
  78.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants 98 participants 202 participants
American Indian or Alaska Native
2
   1.9%
0
   0.0%
2
   1.0%
Asian
12
  11.5%
14
  14.3%
26
  12.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
14
  13.5%
11
  11.2%
25
  12.4%
White
76
  73.1%
73
  74.5%
149
  73.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants 98 participants 202 participants
Sweden 7 7 14
Turkey 14 15 29
United States 80 72 152
United Kingdom 3 4 7
Gestation   [1] 
Mean (Standard Deviation)
Unit of measure:  Weeks of gestation
Number Analyzed 104 participants 98 participants 202 participants
25.7  (1.2) 25.9  (1.1) 25.8  (1.2)
[1]
Measure Description: weeks of gestation
1.Primary Outcome
Title 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)
Hide Description 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 through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group Description:

Infants randomized to the early treatment group will receive "pharmacologic treatment of the PDA" to produce PDA closure.

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

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.)

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
33
  31.7%
38
  38.8%
2.Secondary Outcome
Title Duration of Gavage Feeding Assistance
Hide Description duration of gavage feeding assistance
Time Frame up to 20 weeks of age
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group Description:

Infants randomized to the early treatment group will receive "pharmacologic treatment of the PDA" to produce PDA closure.

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

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.)

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).

Overall Number of Participants Analyzed 104 98
Median (Inter-Quartile Range)
Unit of Measure: days
76
(66 to 104)
80
(61 to 97)
3.Secondary Outcome
Title Incidence of Necrotizing Enterocolitis or Spontaneous Perforation
Hide Description incidence of necrotizing enterocolitis or spontaneous perforation
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
17
  16.3%
19
  19.4%
4.Secondary Outcome
Title the Average Daily Weight Gain
Hide Description the average daily weight gain
Time Frame up to 20 weeks of age
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Mean (Standard Deviation)
Unit of Measure: gm/kg/day
22.5  (4.8) 22.8  (4.6)
5.Secondary Outcome
Title Incidence of Bronchopulmonary Dysplasia or Death
Hide Description incidence of bronchopulmonary dysplasia or death
Time Frame determined between 36-37 weeks corrected age
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
60
  57.7%
56
  57.1%
6.Secondary Outcome
Title Incidence of Death
Hide Description incidence of death
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
20
  19.2%
10
  10.2%
7.Secondary Outcome
Title the Incidence of Persistent Moderate-to-large PDA Shunt 10 Days After Enrollment
Hide Description the incidence of persistent moderate-to-large PDA shunt 10 days after enrollment The echocardiographic studies included two dimensional imaging, M-mode, color flow mapping and Doppler interrogation as previously described. A moderate-to-large PDA was defined by a ductus internal diameter ≥ 1.5mm (or PDA:left pulmonary artery diameter ratio ≥0.5) and one or more of the following echocardiographic criteria: a) left atrium-to-aortic root (LA/Ao) ratio ≥1.6, b) ductus flow velocity ≤2.5m/sec or mean pressure gradient across the ductus ≤8mm, c) left pulmonary artery diastolic flow velocity > 0.2 m/sec, and/or d) reversed diastolic flow in the descending aorta. Ductus that failed to meet these criteria were considered to be “constricted” (small or closed) and not eligible for enrollment or treatment.
Time Frame 10 days after enrollment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
43
  41.3%
78
  79.6%
8.Secondary Outcome
Title the Incidence of Rescue Treatment Eligibility Criteria Met
Hide Description Infants were eligible for rescue PDA drug treatment if they met one or more of the following prespecified “Rescue” criteria: 1) Inotrope-dependent hypotension for at least 3 days. 2) Oliguria that persisted for at least 2 days with no obvious cause, other than the moderate PDA, to explain the condition. 3) Requirement for gavage feedings beyond 35 weeks corrected age due to increased work of breathing. 4) Respiratory support needed after the following postnatal ages that surpassed specific minimal ventilation and FiO2 requirements: >15 days (if still required intubation and FiO2 >0.30), >20 days (if still required intubation and FiO2 ≤0.30; or still required Nasal CPAP or Nasal ventilation and FiO2 >0.30), >30 days (if still required Nasal CPAP or Nasal ventilation and FiO2 0.25-0.30), and >45 days (if still required Nasal CPAP or Nasal ventilation and FiO2 <0.25).
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
32
  30.8%
61
  62.2%
9.Secondary Outcome
Title Number of Infants Receiving ≥ 14 Days of Diuretic Treatment
Hide Description number of infants receiving ≥ 14 days of diuretic treatment
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
36
  34.6%
45
  45.9%
10.Other Pre-specified Outcome
Title Number of Infants Who Received Dopamine for ≥3 Days
Hide Description number of infants who received dopamine for ≥3 days
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
14
  13.5%
25
  25.5%
11.Other Pre-specified Outcome
Title Incidence of Bacteremia
Hide Description incidence of bacteremia
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
31
  29.8%
21
  21.4%
12.Other Pre-specified Outcome
Title Incidence of Pulmonary Hemorrhage
Hide Description incidence of pulmonary hemorrhage
Time Frame through hospital discharge (approximately 6 months unless death occurs first)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Early Treatment Conservative Treatment
Hide Arm/Group 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.

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

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.

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).

Overall Number of Participants Analyzed 104 98
Measure Type: Count of Participants
Unit of Measure: Participants
2
   1.9%
2
   2.0%
Time Frame until hospital discharge (approximately 6 months unless death occurs first)
Adverse Event Reporting Description The definition of serious adverse event in this trial only included the following: Necrotizing enterocolitis and death.
 
Arm/Group Title Early Treatment Conservative Treatment
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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.

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

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.

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).

All-Cause Mortality
Early Treatment Conservative Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   20/104 (19.23%)   10/98 (10.20%) 
Show Serious Adverse Events Hide Serious Adverse Events
Early Treatment Conservative Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   17/104 (16.35%)   19/98 (19.39%) 
Gastrointestinal disorders     
necrotizing enterocolitis  [1]  17/104 (16.35%)  19/98 (19.39%) 
Indicates events were collected by systematic assessment
[1]
NEC
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Early Treatment Conservative Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0 
See detailed limitations in published manuscript
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Ronald Clyman, MD PI
Organization: University of California San Francisco
Phone: 415-443-9305
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01958320     History of Changes
Other Study ID Numbers: RC4
First Submitted: October 4, 2013
First Posted: October 9, 2013
Results First Submitted: October 9, 2018
Results First Posted: November 30, 2018
Last Update Posted: November 30, 2018