| Methods |
Single centre, Singapore (April 1988 to July 2000), randomized controlled trial.
I. Blinding of randomization:
‐yes (computer program). Stratified blocked randomization was used with birth weight (<1000 g and 1000‐1499 g) as the stratification factor.
II. Blinding of intervention:
‐no
III. Complete follow‐up:
‐yes (plan to f/u neurodevelopmental outcome at 2 years of age)
IV. Blind outcome assessment:
‐yes, diagnostic echocardiograms were blinded. |
| Participants |
140 VLBW (<1500 g) preterm infants who had a hemodynamically significant PDA, defined as the presence of any of the following: systolic murmur, hyperactive precordium, wide pulse pressure (diastolic pressure less than half of systolic), hypotension, apnea or rising pCO2, plus a PDA >1.5mm in diameter on a 2‐dimensional echocardiogram. Infants were excluded if they had any major congenital malformation or NEC. |
| Interventions |
Prolonged course: 6‐day course indomethacin (Indocid IV, Merck, West Point, PA): 0.1 mg/kg/dose IV every 24 hours) (n=71).
Short course: 0.2 mg/kg per dose every 12 hours for three doses (n=69).
If the ductus failed to close or relapsed after the first course and was hemodynamically significant, a second course was given after an interval of at least 48 hours from the last dose. The dosing regimen of the second course was the same as that for the first. Surgical ligation was conducted if both courses failed.
Enrolled infants were followed up until death or discharge from the hospital.
To document response scans were repeated 24 to 72 hours after the last dose of the drug. Additional scans were done at the discretion of the physician in charge. |
| Outcomes |
Primary: response to the first indomethacin course. It was defined echocardiographically as:
1) closed: ductus was closed (without relapse) and needed no further treatment;
2) open: ductus still open and hemodynamically significant; and
3) relapsed: ductus relapsed and was hemodynamically significant.
Failure of response means that the ductus was either open or relapsed after treatment.
Secondary: need for a second course of indomethacin, number of surgical ligations, and anticipated side effects: oliguria, increased serum creatinine, decreased serum sodium, brownish gastric aspirates treated with ranitidine, fresh gastric bleeding, and focal gastrointestinal perforation. Side effects were considered to be attributable to indomethacin if occurred within a week of starting treatment.
Other reported outcomes:
ROP (Stage III), NEC (Stage II/III), CLD (supplemental oxygen at 28 days and 36 weeks corrected gestational age), IVH (Grades III, IV). |
| Notes |
Data on potential confounder parameters were also collected: daily fluid intake for the first two weeks, surfactant use, ventilator parameters, pulmonary pathology, antenatal steroids, and culture‐proven sepsis.
Feedings were started early and were not withheld during indomethacin treatment.
The duration of supplemental oxygen was reported as the median, not the mean value. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Low risk |
A ‐ Adequate |
