Prolonged versus short course indomethacin in treatment of patent ductus arteriosus in preterm infants
| Citation | Study group | Study type (level of evidence) | Outcome | Key results | Comments |
|---|---|---|---|---|---|
| Rhodes et al (1988) | 70 preterm infants <1500 g with echocardiographically diagnosed PDA were randomised to either prolonged course indomethacin over 1 week or to short course (2 doses of indomethacin; n = 36). All infants were given 2 doses of indomethacin 0.15 mg/kg 12 hours apart. The prolonged course group (n = 34) received additional 0.1 mg/kg once daily hourly × 5 days. | Prospective randomised controlled trial (level 1b) | Closure after first course | RR 1.11 (95% CI 0.77 to 1.61); RD 0.06 (95% CI −0.16 to 0.29) | No blinding of intervention. No differences in mortality rates. |
| Recurrence of PDA | RR 1.51 (95% CI 0.65 to 3.52); RD 0.10 (95% CI −0.10 to 0.30) | ||||
| Need for surgical ligation | RR 2.12 (95% CI 0.20 to 22.30); RD 0.03 (95% CI −0.06 to 0.13) | ||||
| Hammerman and Aramburo (1990) | 39 infants <1500 g with echocardiographically confirmed PDA were randomised to receive standard indomethacin therapy (0.2 mg/kg/dose 8 hourly), followed by either maintenance indomethacin (0.2 mg/kg once daily × 5 days; n = 20) or equivalent volume of placebo for 5 days (n = 19). | Prospective randomised controlled trial (level 1b) | Closure after first course | RR 1.22 (95% CI 0.90 to 1.66); RD 0.16 (−0.07 to 0.40) | Double blind study. There was no increase in the toxic effects of indomethacin. |
| Recurrence of PDA | RR 0.11 (95% CI 0.01 to 1.84); RD −0.21 (95% −0.41 to −0.01) | ||||
| Need for surgical ligation | RR 0.14 (95% CI 0.02 to 1.00); RD −0.32 (−0.56 to 0.08); NNT 3.0 (95% CI 2 to 12) | ||||
| Rennie and Cooke (1991) | Total of 121 infants <2500 g with clinical signs of PDA were randomised to receive either prolonged course indomethacin (0.1 mg/kg once daily × 6 days; n = 59) or short course (0.2 mg/kg 12 hourly × 3 doses; n = 62). | Prospective randomised controlled trial (level 1b) | Closure after first course | RR 1.16 (95% CI 0.99 to 1.36); RD 0.12 (95% CI −0.01 to 0.25) | No blinding. Echocardiography was not used for assessment of PDA. Higher mortality rate in the prolonged indomethacin group, not directly related to treatment. Majority occurred after the first month. |
| Recurrence of PDA | RR 0.61 (95% CI 0.32 to 1.17); RD −0.12 (95% CI −0.27 to 0.03) | ||||
| Need for surgical ligation | RR 1.58 (95% CI 0.27 to 9.10); RD 0.02 (95% CI −0.05 to 0.09) | ||||
| Tammela et al (1999) | 61 infants of gestational ages 24–32 wk with a PDA confirmed with echocardiography were randomised to receive short course indomethacin (3 doses of 0.2, 0.1, and 0.1 mg/kg in 24 hours; n = 31) or prolonged course (0.1 mg/kg q 24 hourly × 7 days). Echocardiography was performed 3, 9, and 14 days after starting treatment. | Prospective randomised controlled trial (level 1b) | Closure after first course | RR 0.71 (95% CI 0.54 to 0.93); RD −0.27 (−0.46 to −0.08) | Only assessment was blinded. No difference in mortality rates. |
| Need for surgical ligation | Increased need for surgical ligation in the prolonged group [RR 4.65 (95% CI 1.09 to 19.78); RD 0.24 (95% CI 0.05 to 0.42); NNH 4.0 (95% CI 2 to 20)] | ||||
| Recurrences needing treatment | RR 1.03 (95% CI 0.37 to 2.85); RD 0.01 (−0.19 to 0.21) | ||||
| Lee et al (2001) | Infants ⩽1500 g with a symptomatic PDA greater or equal to 1.5 mm on echocardiography were randomised to conventional indomethacin (0.2 mg/kg/dose q 12 hourly × 3 doses; n = 70) or prolonged low dose course indomethacin (0.1 mg/kg q 24 hourly × 6 doses; n = 70). | Prospective randomised controlled trial (level 1b) | Closure after first course | Relative risk (RR) 1.02; 95% CI 0.87 to 1.27; risk difference (RD) 0.01; 95% CI −0.14 to 0.17. | No blinding of intervention. Intention to treat analysis. PDA diagnosis by echocardiography. No difference in mortality rates. |
| Need for surgical ligation of PDA | RR 0.62 (95% CI 0.27 to 1.39); RD −0.07 (−0.19 to 0.05) |