[Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm infants]. Oral ibuprofen and indomethacin for treatment of patent ductus arteriosus in premature infants: a randomized trial at Ramathibodi Hospital. A comparison of oral ibuprofen and intravenous indomethacin for closure of patent ductus arteriosus in preterm infants. Comparison of oral ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. [Comparison of the efficacy of ibuprofen and indomethacin in the treatment of patent ductus arteriosus in prematurely born infants]. Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial. Ibuprofen versus continuous indomethacin in premature neonates with patent ductus arteriosus: is the difference in the mode of administration? Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants.
Persistent patent ductus arteriosus (PDA) is a common entity in preterm infants. The most commonly used pharmacological treatment to close the ductus is indomethacin but it can affect cerebral, renal and mesenteric blood flow. Ibuprofen has recently been shown to be effective in closing PDA with fewer hemodynamic effects. In this study we compared the safety and efficacy of ibuprofen and indomethacin in the treatment of PDA in preterm infants.
                A randomized trial was performed. Premature infants with symptomatic PDA confirmed by echocardiography in the first week of life and who required respiratory support were included. The patients were randomly assigned to receive either intravenous indomethacin or ibuprofen. The rate of ductal closure, need for additional treatment, complications, and clinical course were evaluated.
                Twenty-four patients were treated with indomethacin and 23 with ibuprofen. The clinical characteristics before treatment were similar in both groups. Both treatments were effective in closing PDA (87.5% in the indomethacin group and 82.6% in the ibuprofen group). The two cohorts did not differ in the rate of reopening, need for a second pharmacologic treatment, or surgical ductal ligation. No patient in the ibuprofen group developed gastrointestinal adverse effects, but two infants in the indomethacin group had isolated bowel perforation and one had necrotizing enterocolitis. Transient renal dysfunction developed in seven patients (29%) in the indomethacin group versus two (9%) in the ibuprofen group. Transient renal insufficiency was found in one patient in the indomethacin group and in none in the ibuprofen group. The rate of other complications was similar in both groups.
                In our trial ibuprofen was as effective as indomethacin in closing PDA. No significant differences were found in the incidence of complications but fewer renal complications and no gastrointestinal complications were found in the ibuprofen group. Ibuprofen given intravenously to premature newborn infants is a proven treatment for patent ductus arteriosus (PDA). The efficacy of ibuprofen is comparable to indomethacin in many clinical trials with fewer renal side effects. However, the intravenous form of ibuprofen is not available in Thailand, whereas, the oral suspension form is widely used for antipyretic treatment in children. Therefore, the authors investigated the possibilities of using oral ibuprofen for the treatment of PDA in premature newborn infants.
                To assess whether oral ibuprofen at 10 mg/kg/dose daily for 3 days was as effective as indomethacin to treat symptomatic PDA in premature infants and to compare the side effects of oral ibuprofen to indomethacin.
                Eighteen premature infants with gestational ages less than 34 weeks born at Ramathibodi Hospital who developed symptomatic PDA were randomly assigned to receive three doses of either indomethacin (oral or intravenous administration 0.2 mg/kg/dose for three doses given at 12 hourly intervals or oral ibuprofen (10 mg/kg/dose for three doses given at 24 hourly intervals). The rates of ductal closure, infants' clinical courses, side effects and complications were recorded.
                Birth weight, gestational age, gender, age onset and number of infants who had respiratory distress syndrome were similar in both groups, PDA was closed in 7 of 9 infants given ibuprofen (78%) and in 8 of 9 infants given indomethacin (89%) (p > 0.05). The mean plasma concentration of ibuprofen was 28.05 microg/ml at 1 hour after the third dose. Neonates in the ibuprofen group had more urine output. However, the increment of serum BUN and creatinine were not significantly different in both groups. There were no significant differences in duration of ventilator support as well as number of patients with bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and death in both groups.
                Oral ibuprofen therapy is as effective as indomethacin for the treatment of PDA in premature infants and seems to have fewer renal side effects. Indomethacin is widely accepted as the treatment for patent ductus arteriosus (PDA) in preterm infants but it has various side effects. Ibuprofen is the alternative treatment and believed to be less likely to induce side effects.
                To compare efficacy and side effects of ibuprofen versus indomethacin treatment for symptomatic patent ductus arteriosus (PDA) in preterm infants.
                The authors studied 30 infants (gestational age < or = 35 weeks, aged < or = 10 days) who were diagnosed as having symptomatic PDA confirmed by echocardiogram. The infants were randomly assigned to receive three intravenous doses of indomethacin given at 12-hour intervals or three doses of ibuprofen given at 24-hour intervals, starting within ten days of life. The demographic data, rate of clinical closure, need for additional treatment, side effects, complications and the infants' clinical course were recorded within 28 days.
                The rate of ductal closure was similar with the two treatment regimes. Ductal closure occurred in 7 of 15 infants given ibuprofen (46.67%) and 10 of 15 infants given indomethacin (66.67%). (Relative risk 0.669; 95% confidence interval, 0.328 to 1.364; p = 0.462) The number of infants who needed a second pharmacologic treatment was not significantly different between the two groups, (6 cases in the ibuprofen group, 5 cases in the indomethacin group) but surgical ligation was performed in two cases in the indomethacin group. There was a significant difference in using the diuretic drug (furosemide) in the indomethacin group (11 cases), compared to the ibuprofen group (3 cases), (p = 0.009). More cases of necrotizing enterocolitis were seen in the indomethacin group (66.67% compared to 40% in the ibuprofen group) but there was no statistically significant difference.
                Ibuprofen has the same efficiency as indomethacin for the treatment of symptomatic patent ductus arteriosus in preterm infants and less likely to induce necrotizing enterocolitis and renal toxicity than indomethacin. Intravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants.
                Thirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants' clinical course were recorded.
                The ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P > 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P < 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC.
                Oral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC. Indomethacin (INDO) and, more recently, ibuprofen (IBU) have been used to treat haemodynamically significant patent ductus arteriosus (PDA) in preterm infants. Both are cyclo-oxygenase blockers, but seem to have a different influence on regional circulation. In a prospective, randomised, controlled study, we compared INDO and IBU with regard to efficacy and safety for the early non-invasive treatment of PDA. Doppler echocardiography was used to study 232 preterm infants (gestational age 23-34 weeks) with respiratory distress syndrome of whom 175 had persistent, haemodynamically significant PDA at 48-72 h of life. They were randomised to receive three intravenous doses of either INDO (0.2 mg/kg, at 12 h intervals) or IBU (a first 10 mg/kg dose followed by two doses of 5 mg/kg at 24 h intervals), recording rate of ductal closure, need for additional treatment, side-effects and clinical course. The efficacy of the pharmacological treatment was similar in the two groups (56/81, 69% INDO; 69/94, 73% IBU). Patients treated with INDO showed a significant increase in serum creatinine (89 +/- 24 versus 82 +/- 20 mmol/l, P = 0.03) and a near-significant tendency for a lower fractional excretion of sodium (3 +/- 3 versus 4 +/- 2%, P = 0.08); moreover, 12/81 (15%) INDO patients versus 1/94 (1%) IBU patients became oliguric (< 1 ml/kg per h) during treatment (P = 0.017).
                Our findings confirm that, by comparison with indomethacin, ibuprofen has fewer effects on renal function in terms of urine output and fluid retention, with much the same efficacy and safety in closing patent ductus arteriosus in preterm infants with respiratory distress syndrome. In particular, no increased incidence of intracranial haemorrhage was observed after ibuprofen treatment. To assess the efficacy and safety of early treatment with ibuprofen (IBU) and indomethacin (INDO) of patent ductus arteriosus in preterm infants. Prospective study with blind trial.
                We studied 35 preterm infants (19 treated with INDO, 16 IBU) (gestation age <33 and birth weight < 1500 g), who had an echocardiographicaly confirmed patent ductus arteriosus (PDA). The infants were randomly assigned in two groups to receive INDO (0.2-0.2-0.2 mg/kg) or IBU (10-5-5 mg/kg) in first 72 hours of life (average 2 days of life). The rate of ductal closure, the need for surgical ligation, side effects, complications, and the infants clinical course were recorded.
                The rate of ductal closure was similar in two groups (15/19, 80% INDO; 11/16, 69% IBU). 27 infants (15 INDO, 12 IBU) were treated per protocol (3 doses). For remaining 8 infants we stopped treatment due to side effects. In the IBU group the main reason to stop treatment was pulmonary hemorrhage (3/16, 19%) and pulmonary hypertension (1/16, 6%), but in the INDO group it was increased serum creatinine and urea nitrogen concentrations (3/19, 16%) and intraventricular hemorrhage (IVH IV) grade (1/19 5%). In IBU group vs. INDO, urine output decreased (p=0.02), but never before below the level of oliguria (defined as urine output below 1 ml/kg/h). Risk of necrotizing enterocolitis (NEC) grade II was similar in two groups, but only patients treated with INDO showed intestinal perforations (p=ns). They received also postnatal hydrocortisone and we showed near significant tendency (p=0.06) for intestinal perforation in patients treated with INDO and hydrocortisone. There were no significant differences with respect to IVH or PVL between the groups.
                The efficacy of ibuprofen and indomethacin in PDA treatment is similar. Treatment of ibuprofen and indomethacin may cause transient renal dysfunction: diminished urine output and increase of serum creatinine and urea nitrogen concentrations. Indomethacin, especially with concomitant treatment with hydrocortisone, may increase the risk of intestinal perforation. To date there is no firm conclusion as to the efficacy and safety of ibuprofen compared with indometacin for patent ductus arteriosus (PDA) closure in extremely premature infants.
                To conduct a randomised controlled trial to better address this problem.
                119 infants (gestational age < or =28 weeks) with respiratory distress syndrome and PDA confirmed by echocardiography were randomly assigned to receive either indometacin (0.2 mg/kg) or ibuprofen (10 mg/kg), starting at <24 hours of life, followed by half these first doses within 48 hours at 24-hour intervals if indicated by echocardiographic PDA flow pattern.
                The PDA closure rate and the doses of drug (mean (SD)) were similar in both groups: 53/60 (88.3%) and 1.9 (1.5) mg/kg in infants given ibuprofen, and 52/59 (88.1%) and 1.9 (1.7) mg/kg in infants given indometacin. No significant difference was found in the numbers of infants requiring surgical ligation, and the levels of post-treatment serum creatinine and urea nitrogen between the two groups. Although not significantly different, more infants (9/59 (15.3%)) treated with indometacin tended to develop oliguria (<1 ml/kg/h) than those treated with ibuprofen (4/60 (6.7%)). There were no significant differences in side effects or complications between the two groups.
                Ibuprofen is as effective as indometacin for the early-targeted PDA treatment in extremely premature infants, without increasing the incidence of complications. When the echocardiographic PDA flow pattern was used as a guide for PDA treatment, fewer doses of drugs were needed to achieve acceptable closing rates. Ibuprofen has been proposed as a preferential alternative to indomethacin in treating patent ductus arteriosus (PDA), because it is purported to have less renal, mesenteric, and cerebral vasoconstrictive effects. However, short and long-term safety concerns regarding ibuprofen remain. Continuous slow infusion of indomethacin also eliminates peripheral vasoconstriction and may thus offer similar benefits to ibuprofen without safety concerns. In this study, our objective was to show that treating a PDA with continuous indomethacin is similar to ibuprofen in its effect on urine output, renal function, and blood flow velocities in the renal, superior mesenteric, and anterior cerebral arteries. Sixty four prematures with PDA were randomly, prospectively assigned to either treatment. PDA closure rates were similar (74 versus 59%; p = 0.123). Nine indomethacin-treated babies (29%) versus twelve ibuprofen babies (38%) underwent repeated therapy (p = 0.656). Two indomethacin and four ibuprofen infants required surgical ligation (p = 0.672). Serum creatinine, oliguria, estimated glomerular filtration rate, and fractional excretion of sodium were similar in both groups, as were blood flow velocity parameters in the vessels studied. There were no differences in necrotizing enterocolitis, BPD, intraventricular hemorrhage, and/or retinopathy of prematurity. In conclusion, PDA treatment with either continuous indomethacin infusion or ibuprofen was equally devoid of adverse renal effects and/or peripheral vasoconstrictive effects. Patent ductus arteriosus (PDA) is commonly found in very low-birthweight (VLBW) infants. The presence of respiratory distress syndrome (RDS) is also associated with increased frequency of significant PDA. Intravenous indomethacin has been used to treat and to prevent PDA in premature infants since 1976. However, concern remains regarding the safety of indomethacin, which affects renal, gastrointestinal and cerebral perfusion. Intravenous ibuprofen has recently been used to treat and to prevent PDA premature infants with PDA without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. The aim of the present study is to compare intravenous ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of PDA in preterm infants.
                A total of 63 preterm infants with RDS who had a birthweight of < or =1500 g and gestational age of < or =32 weeks, were enrolled in the present study. All patients were treated with nasal continuous positive airway pressure with additional oxygen supply in inspired air>30%, or with mechanical ventilation. The patients' serum platelet counts were>100,000/uL, and serum creatinine values were <1.5 mg/dL. There were no 3-4 grade intraventricular hemorrhages before randomization, and all patients were aged 2-7 days and had echo-cardio-graphic evidence of significant PDA. Patients were randomized into two groups: the first group of neonates (group A, n = 32) received intravenous ibuprofen lysine 10 mg/kg, followed by 5 mg/kg after 24 and 48 h; the second group (group B, n = 31) received intravenous indomethacin 0.2 mg/kg every 12 h for three doses.
                Patent ductus arteriosus closed in 27 patients from the ibuprofen group (84.4%) and in 25 patients from the indomethacin group (80.6%). PDA reopened in three patients from the ibuprofen group (9.4%) and in three patients from the indomethacin group (9.7%). One patient in the ibuprofen group and two patients in the indomethacin group required ductal ligation. Serum creatinine and blood urea nitrogen (BUN) concentrations were lower in the ibuprofen group than in the indomethacin group. Urine output and creatinine clearance values were higher in the ibuprofen group than in the indomethacin group.
                Ibuprofen therapy is as efficacious as indomethacin for the treatment of PDA in preterm infants. Infants treated with ibuprofen have higher creatinine clearance and urine output and lower serum creatinine and BUN values than infants treated with indomethacin.
Ibuprofen is as effective as indomethacin in closing a PDA and reduces the risk of NEC and transient renal insufficiency. Given the reduction in NEC ibuprofen currently appears to be the drug of choice. Oro-gastric administration of ibuprofen appears at least as effective as iv administration. Too few patients have been enrolled in studies assessing the effectiveness of a high dose of ibuprofen versus the standard dose and early versus expectant administration of ibuprofen to make recommendations. Studies are needed to evaluate the effect of ibuprofen compared with indomethacin treatment on longer-term outcomes in infants with PDA.