| Methods |
Single centre, Israel (dates not given), randomized, double‐blind, placebo‐controlled trial.
I. Blinding of randomization:
‐ yes (pharmacist responsible for random assignment)
II. Blinding of intervention: yes
III. Complete follow‐up: yes
IV. Blind outcome assessment:
‐ yes |
| Participants |
39 premature VLBW infants (< 1500 grams). BW (mean +/‐ SD) 1099 +/‐ 435 g, GA 28 +/‐ 3 wk, age at indomethacin therapy 9 +/‐ 4 days (indomethacin group) versus BW 1040 +/‐ 394 g, GA 27 +/‐ 7 wk, age at indomethacin therapy 10 +/‐ 5 days (placebo group).
Diagnosis of clinically significant PDA was made by clinicians (murmur plus any two of the following: bounding pulses, diastolic pressure equal or less than 25 mmHg, cardiomegaly or pulmonary plethora on chest X‐ray) and confirmed by echocardiogram (M mode and pulsed Doppler).
Exclusion criteria: older than 21 days postnatal age, platelet count < 80,000/uL, renal failure, persistent fetal circulation, any other congenital heart disease. |
| Interventions |
Initially, all infants received standard indomethacin therapy (3 doses of 0.2 mg/kg/dose IV every 12 hours). Prolonged course: additional 0.2 mg/kg/day IV for 5 days (n=20). Short course: equivalent volume of placebo (sterile water) for 5 days (n=19). Infants received first dose of indomethacin at a mean age of 9‐10 days. Initial and subsequent dosages of indomethacin equaled 1 week of therapy.
Alveolar‐arterial gas pressure difference, "cardiovascular distress score" were calculated. Measurements of 6‐keto‐prostaglandin F1 alpha were also done. Second echocardiogram was done within 48 hours after completion of the 7‐day course therapy. If PDA murmur recurred, a repeat echocardiogram was also done. |
| Outcomes |
Primary: decrease in the incidence of surgical ligation
Other: non‐response to treatment, PDA re‐opening, prostaglandin levels, renal function, ROP, NEC, IVH, BPD (outcome assessed, but no definitions given), oxygen therapy at home, death. |
| Notes |
Re‐treatment after intervention included both ligation and indomethacin (dosing not reported) |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Low risk |
A ‐ Adequate |
