| Methods |
Two centres, Finland (dates not given), randomized controlled trial without the use of a placebo.
I. Blinding of randomization:
‐unclear
II. Blinding of intervention: no
III. Complete follow‐up: yes
IV. Blind outcome assessment: no |
| Participants |
61 premature infants (24 to 32 weeks estimated GA).
BW (mean +/‐ SD) 1094 +/‐ 298 g, GA 27.3 +/‐ 1.9 wk, age at indomethacin therapy 3.1 +/‐ 1.7 days (prolonged low dose group) versus BW 1154 +/‐ 388 g, GA 27.9 +/‐ 2.3 wk, age at indomethacin therapy 4.3 +/‐ 4.4 days (short standard dose group). Infants had hemodynamically significant PDA (at least 3 of 6 clinical signs: heart murmur, increased precordial impulse, bounding pulses, tachycardia, unexplained deterioration of the respiratory status, and cardiomegaly or pulmonary edema by chest X‐ray ) with continuous left to right shunt by echocardiography.
Indomethacin was considered the treatment of choice by the attending physician.
Exclusion criteria: ductal‐dependent heart defect, pulmonary hypertension or bidirectional shunt, oliguria (urine output < 1 ml/kg/h for more than 6 hours), platelet count <60 x 10^9/L or bleeding diathesis, bilirubin level > 200 umol/L (11.7 mg/dL), clinical or radiologic evidence for NEC. |
| Interventions |
Prolonged course: IV indomethacin at 0.1 mg/kg/dose every 24 hours for 7 days (n=30). Short course: 3 doses of IV indomethacin at 12 hour intervals (0.2, 0.1, and 0.1 mg/kg/dose) (n=31).
Infants received first dose of indomethacin at a mean age of 3‐4 days.
Echocardiograms were obtained for all infants with clinical signs of a PDA. To detect silent PDAs, echocardiography was used for all infants treated with ventilators daily during the first 3 to 4 days of life and later in cases with an increased need for ventilatory support. Echocardiography was done 3, 9, and 14 days after the first dose of indomethacin was administered and in all cases where an unsuccessful ductal closure or PDA reopening was suspected on clinical evaluation. Side effects were also monitored. |
| Outcomes |
Primary: ductal closure confirmed by echocardiogram on the ninth day after first dose of indomethacin
Secondary: PDA reopening, retreatment with indomethacin, surgical ligation, mortality, BPD (oxygen requirement and CXR changes at 36 wk PCA), ROP, IVH, cystic PVL, duration of assisted ventilation, oxygen supplementation, inotropics use, length of hospital stay, and adverse events (urine output < 1 ml/kg/h, creatinine > 150 umol/L, BUN > 3.6 mmol/L, bleeding diathesis, thrombocytopenia (<60 x 10^9/L), GI hemorrhage, NEC, severe adverse event (at least one of the following: severe bleeding, symptomatic oliguria, NEC with intestinal perforation). |
| Notes |
Echocardiograms were classified in 2 categories: presence or absence of a clinically and hemodynamically significant PDA requiring treatment.
Retreatment (doses not specified) with indomethacin was given when the PDA reopened. Final closure rates were better for those infants who received the short course initially. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment? |
Unclear risk |
B ‐ Unclear |
