Effects of Prophylactic Oxytocin on Bleeding Outcomes in Women Undergoing Dilation and Evacuation: A Randomized Controlled Trial
Obstetrics and gynecology. 2019
OBJECTIVE To estimate whether routine use of intravenous oxytocin decreases the frequency of interventions to control excess blood loss during dilation and evacuation (D&E). METHODS In this multisite, randomized, double-blind, placebo-controlled trial, women undergoing D&E at 18-24 weeks of gestation received 30 units of oxytocin in 500 mL of intravenous fluid or 500 mL of intravenous fluid alone initiated on speculum placement. The primary outcome was the frequency of interventions to control excess bleeding. A sample size of 75 patients per group was needed to detect a 15% decrease in intervention from 20% to 5% with 80% power and two-sided alpha 0.05. Secondary outcomes included measured blood loss, complications, procedure duration, postoperative pain, and patient satisfaction. RESULTS From November 2014 to February 2018, we screened 337 women and randomized 160 to receive prophylactic oxytocin (n=82) or placebo (n=78). Demographic characteristics were similar between groups. The frequency of interventions for bleeding, our primary outcome, was 7.3% in the oxytocin group vs 16.7% in the placebo group, difference of 9.4% (95% CI -21.0% to 1.9%). Interventions primarily included uterine massage and uterotonic administration. Among our secondary outcomes, median measured blood loss was lower in the oxytocin group at 152 (interquartile range 98-235) mL vs 317 (interquartile range 168-464) mL (95% CI 71.6-181.5). Frequency of hemorrhage, defined as blood loss of 500 mL or more and 1,000 mL or more, was lower in the oxytocin group at 3.7% vs 21.8%, difference of 18% (95% CI -29 to -6.9%) and 1.2% vs 10.3%, difference of 9.0% (95% CI -17 to -0.7%), respectively. Procedures were shorter in the oxytocin group at a median of 11.0 (interquartile range 8.0-14.0) vs 13.5 (interquartile range 10.0-19.0) minutes in the placebo group (95% CI 1.0-4.0). We found no differences in the frequency of nonhemorrhage complications, pain scores, or satisfaction scores between groups. CONCLUSION Prophylactic use of oxytocin during D&E at 18-24 weeks of gestation did not decrease the frequency of interventions to control bleeding. However, oxytocin did decrease blood loss and frequency of hemorrhage. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, www.clinicaltrials.gov, NCT02083809.
Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP
Journal of medical economics. 2019;:1
AIMS: Prophylaxis with standard-acting recombinant factor IX (rFIX) in hemophilia B patients requires frequent injections. Extended half-life (EHL) products allow for prolonged dosing intervals and so reduce this treatment burden. Three technologies are employed to extend the half-life of FIX; glycopegylation, Fc-fusion, and albumin fusion. rIX-FP is a novel albumin fusion protein, which allows for a prolonged dosing interval of up to 14 days. A systematic review and indirect statistical comparison was performed to evaluate the efficacy of both EHL and standard-acting rFIX products compared with rIX-FP in Phase III trials for prophylaxis in adult hemophilia B patients. MATERIALS AND METHODS A systematic search was conducted in both EMBASE and PubMed to identify Phase III trials of prophylactic rFIX treatment in previously treated, hemophilia B patients aged ≥12 years (FIX: ≤2%). Annualized bleeding rate (ABR), spontaneous ABR (AsBR), and joint ABR (AjBR) data were extracted from each study. A z-test was performed using the mean of each parameter, and the mean difference in outcome between studies was calculated. RESULTS Seven articles investigating six rFIX products were identified. Median ABR, AsBR and AjBR ranged from 0-3.0, 0-1.0, and 0-1.1 (means 0.8-4.26, 0.13-2.6, and 0.34-2.85), respectively. rIX-FP achieved lowest median and mean values in all three parameters. Z-tests showed that mean ABR was significantly lower for rIX-FP 7-day prophylaxis compared with the majority of standard-acting and other EHL rFIX products. LIMITATIONS The low number of appropriate trials available for comparison limits the quantity of data available for comparison and restricts the use of methods of adjustment for variance in study design or patient characteristics. However, these limitations are shared with similar analyses published in this field. CONCLUSION This indirect comparison of Phase III trials indicates that rIX-FP efficacy compares favorably versus other rFIX products for prophylaxis in hemophilia B.
Efficacy and safety of prophylactic treatment with plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency
UNLABELLED Congenital factor XIII (FXIII) deficiency is an extremely rare, potentially life-threatening bleeding disorder. Routine prophylactic management is recommended for individuals with clinically relevant FXIII deficiency. This prospective, multicentre, open-label study evaluated the long-term efficacy and safety of prophylactic infusions of FXIII concentrate (human) 40 IU kg(-1) in patients with congenital FXIII deficiency. FXIII concentrate (human) was administered every 4 weeks for 12 months. Dosing was adjusted to maintain trough FXIII activity levels of 5-20%. Logistical and ethical constraints precluded use of a placebo control group. Annualized incidence of spontaneous bleeding was compared with historical rates; safety was assessed as a secondary objective. Forty-one patients were enrolled and completed the study. The annualized rate for spontaneous bleeding episodes requiring FXIII treatment was 0.000 episodes per patient-year (95% CI: 0.000; 0.097). The study met its primary endpoint: the upper limit of the 95% CI was substantially below the historical rate of 2.5 bleeding episodes per patient-year. Five spontaneous bleeding episodes (involving three patients; none requiring FXIII treatment) and eight trauma-related bleeding episodes (two requiring FXIII treatment) occurred. Five patients had surgery during the study, only one of whom required FXIII treatment for post-surgical bleeding. Most patients (>85%) had trough FXIII activity levels >10%. No patient discontinued treatment due to an adverse event. No adverse events related to thromboembolism or viral transmission were reported. Prophylactic treatment with FXIII concentrate (human) was well tolerated and prevented spontaneous bleeding episodes that were serious enough to require treatment with FXIII-containing product. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov/ct2/show/NCT00885742. 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.
Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions
Journal of Pediatrics. 1996;129((1):):89-96.
OBJECTIVES To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. STUDY DESIGN A double-blind, randomized, controlled trial. SUBJECTS Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment. RESULTS Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores. CONCLUSIONS Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy.