Trial Outcomes & Findings for Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus (NCT NCT01958320)
NCT ID: NCT01958320
Last Updated: 2018-11-30
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
202 participants
Primary outcome timeframe
through hospital discharge (approximately 6 months unless death occurs first)
Results posted on
2018-11-30
Participant Flow
Participant milestones
| Measure |
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.
pharmacologic treatment of the PDA: Following randomization, infants will be treated with medications used to produce PDA closure.
|
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.
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 Study
STARTED
|
104
|
98
|
|
Overall Study
COMPLETED
|
104
|
98
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus
Baseline characteristics by cohort
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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
n=202 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
104 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
8.1 days after birth
STANDARD_DEVIATION 2.1 • n=5 Participants
|
8.3 days after birth
STANDARD_DEVIATION 2.3 • n=7 Participants
|
8.2 days after birth
STANDARD_DEVIATION 2.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
25 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
79 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
76 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
14 participants
n=5 Participants
|
15 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=5 Participants
|
72 participants
n=7 Participants
|
152 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Gestation
|
25.7 weeks of gestation
STANDARD_DEVIATION 1.2 • n=5 Participants
|
25.9 weeks of gestation
STANDARD_DEVIATION 1.1 • n=7 Participants
|
25.8 weeks of gestation
STANDARD_DEVIATION 1.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)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)
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
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)
|
33 Participants
|
38 Participants
|
SECONDARY outcome
Timeframe: up to 20 weeks of ageduration of gavage feeding assistance
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Duration of Gavage Feeding Assistance
|
76 days
Interval 66.0 to 104.0
|
80 days
Interval 61.0 to 97.0
|
SECONDARY outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)incidence of necrotizing enterocolitis or spontaneous perforation
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Incidence of Necrotizing Enterocolitis or Spontaneous Perforation
|
17 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: up to 20 weeks of agethe average daily weight gain
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
the Average Daily Weight Gain
|
22.5 gm/kg/day
Standard Deviation 4.8
|
22.8 gm/kg/day
Standard Deviation 4.6
|
SECONDARY outcome
Timeframe: determined between 36-37 weeks corrected ageincidence of bronchopulmonary dysplasia or death
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Incidence of Bronchopulmonary Dysplasia or Death
|
60 Participants
|
56 Participants
|
SECONDARY outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)incidence of death
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Incidence of Death
|
20 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 10 days after enrollmentthe 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.
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
the Incidence of Persistent Moderate-to-large PDA Shunt 10 Days After Enrollment
|
43 Participants
|
78 Participants
|
SECONDARY outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)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).
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
the Incidence of Rescue Treatment Eligibility Criteria Met
|
32 Participants
|
61 Participants
|
SECONDARY outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)number of infants receiving ≥ 14 days of diuretic treatment
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Number of Infants Receiving ≥ 14 Days of Diuretic Treatment
|
36 Participants
|
45 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)number of infants who received dopamine for ≥3 days
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Number of Infants Who Received Dopamine for ≥3 Days
|
14 Participants
|
25 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)incidence of bacteremia
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Incidence of Bacteremia
|
31 Participants
|
21 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: through hospital discharge (approximately 6 months unless death occurs first)incidence of pulmonary hemorrhage
Outcome measures
| Measure |
Early Treatment
n=104 Participants
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.
|
Conservative Treatment
n=98 Participants
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).
|
|---|---|---|
|
Incidence of Pulmonary Hemorrhage
|
2 Participants
|
2 Participants
|
Adverse Events
Early Treatment
Serious events: 17 serious events
Other events: 0 other events
Deaths: 20 deaths
Conservative Treatment
Serious events: 19 serious events
Other events: 0 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Early Treatment
n=104 participants at risk
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.
|
Conservative Treatment
n=98 participants at risk
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).
|
|---|---|---|
|
Gastrointestinal disorders
necrotizing enterocolitis
|
16.3%
17/104 • until hospital discharge (approximately 6 months unless death occurs first)
The definition of serious adverse event in this trial only included the following: Necrotizing enterocolitis and death.
|
19.4%
19/98 • until hospital discharge (approximately 6 months unless death occurs first)
The definition of serious adverse event in this trial only included the following: Necrotizing enterocolitis and death.
|
Other adverse events
Adverse event data not reported
Additional Information
Ronald Clyman, MD PI
University of California San Francisco
Phone: 415-443-9305
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place