Activated protein C as disease-modifying therapy in antenatal preeclampsia: An open-label, single arm safety and efficacy trial.
Pregnancy Hypertens
; 13: 121-126, 2018 Jul.
Article
em En
| MEDLINE
| ID: mdl-30177038
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. STUDYDESIGN:
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 OUTCOMEMEASURES:
Primary safetyoutcome:
incidence of peripartum bleeding; primary efficacyoutcome:
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⯵g/kg/hr for ≤96â¯h antenatally). No safety issues were identified. There was a marginal prolongation in eligibility-to-delivery intervals for women receiving rhAPC (Mantel-Cox pâ¯=â¯0.052; Gehan-Breslow-Wilcoxon pâ¯=â¯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 >100â¯mL/h during the infusion, Fisher's exact pâ¯=â¯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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pré-Eclâmpsia
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Cuidado Pré-Natal
/
Proteína C
/
Fibrinolíticos
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
/
Pregnancy
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article