1. Activated protein C as disease-modifying therapy in antenatal preeclampsia: An open-label, single arm safety and efficacy trial.
- Author
-
von Dadelszen, Peter, Magee, Laura A., Benton, Samantha J., Hu, Yuxiang, Ansermino, J. Mark, Carleton, Bruce, Carter, Cedric, Douglas, M. Joanne, Janssen, Patricia A., Lee, Shoo K., Leung, Peter C.K., Li, Jing, MacNab, Ying, Payne, Beth A., Peng, Gang, Rodger, Marc, Skoll, M. Amanda, Synnes, Anne, Walley, Keith R., and Russell, James A.
- Subjects
PREECLAMPSIA diagnosis ,FIBRINOLYTIC agents ,BLOOD proteins ,CHILDBIRTH ,CLINICAL trials ,COMPARATIVE studies ,HEMORRHAGE ,RESEARCH methodology ,MEDICAL cooperation ,PREECLAMPSIA ,PRENATAL care ,PUERPERAL disorders ,RECOMBINANT proteins ,RESEARCH ,TIME ,EVALUATION research ,TREATMENT effectiveness ,SEVERITY of illness index ,PARENTERAL infusions - Abstract
Objectives: Preeclampsia is characterized by maternal systemic inflammation and coagulation activation, akin to the sepsis syndrome. Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) may modify disease progression to safely prolong pregnancies and improve perinatal outcomes. Both maternal and perinatal risks are highest remote from term.Study Design: Open-label, single arm safety and efficacy trial of rhAPC in consenting pregnant women with severe early-onset preeclampsia. Disease severity-matched rhAPC-naïve controls were identified from an existing database. An additional six women were recruited as biomarker controls.Main Outcome Measures: Primary safety outcome: incidence of peripartum bleeding; primary efficacy outcome: duration of pregnancy after enrolment.Results: Twelve (31.6%) of 38 eligible women consented; 3 did not receive the infusion due to staffing. Therefore, 9 women received rhAPC (24 μg/kg/hr for ≤96 h antenatally). No safety issues were identified. There was a marginal prolongation in eligibility-to-delivery intervals for women receiving rhAPC (Mantel-Cox p = 0.052; Gehan-Breslow-Wilcoxon p = 0.049). Compared with both the pre-infusion phase in the rhAPC-treated women themselves and with fullPIERS rhAPC-naïve women, rhAPC was associated with increased urine output during the infusion (6/9 vs 1/9 had urine output >100 mL/h during the infusion, Fisher's exact p = 0.003).Conclusions: These data support further investigation of APC in women with severe early-onset preeclampsia; recombinant and purified human APC is available. In addition, these data will inform the design and implementation of randomized controlled trials aiming to modify and/or moderate the proinflammatory and proacoagulant state of preeclampsia. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF