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The purpose of this study is to determine whether a commercially available anti-digoxin antibody, Digibind, can delay delivery in patients with severe pre-eclampsia. If so, this would allow more time for maternally administered steroids to prevent the development of respiratory complications in premature infants.
Full description
Preeclampsia (PE) is a serious complication of third trimester pregnancy manifested by high blood pressure, proteinuria, edema, encephalopathy sometimes with seizures, and hepatic failure. There is no known specific treatment, although palliative measures such as antihypertensive drugs, magnesium, steroids and early delivery improve outcomes. Multiple abnormalities have been demonstrated in PE but the relation of these abnormalities to the cause, pathophysiology and treatment is unknown. One of these abnormalities is elevation in the circulating level of a "digoxin-like" factor (EDLF), an unknown substance that cross reacts with digoxin antibodies and inhibits Na,K ATPase. An extensive literature supports the hypothesis that increased levels of EDLF may be a causative factor in the pathogenesis of hypertension. Increased levels of this factor are found both in maternal and fetal blood, both in normal pregnancy, and in pregnancy complicated by PE. Levels of this factor are higher in PE than in normal pregnancy suggesting it might play a role in the pathophysiology of PE.
Digibind (Glaxo Smith Kline) is a commercially available FAB fragment, antidigoxin antibody approved for the treatment of digoxin intoxication. In experimental models of hypertension with elevated EDLF levels, Digibind has been shown to lower blood pressure, suggesting that the antibody cross reacts with EDLF. These observations have led to the hypothesis that Digibind might ameliorate some of the manifestations of PE, especially the hypertension. Based on an extensive pre-clinical literature supporting that hypothesis, and encouraging results in 8 cases, a clinical trial is planned to test the effect of Digibind in severe PE. The study is a multi- site, parallel, double blind, placebo controlled, randomized trial. After randomization, 50 patients will be given the usual treatment for severe PE, plus study drug (Digibind or placebo) every six hours, for 48 hours. The study may be terminated during the treatment period for standard indications for early delivery.
Data collection will include: delivery latency, maternal blood pressure, antihypertensive use, renal function, hepatic function, CBC and platelet count, and umbilical artery blood flow by color doppler. Standard maternal and fetal monitoring will be followed. Newborn assessment will include: status at birth, APGAR score, NICU length of stay, respirator use and duration, and any medical complications. Adverse events will be recorded.
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Inclusion criteria
A subject with a diagnosis of severe preeclampsia will be eligible for inclusion if she meets the following criteria:
In the opinion of the investigator delivery is considered to be probably required within a 72 hour time period and, therefore, corticosteroid administration is needed.
Meets both American College of Obstetricians (ACOG) criteria for preeclampsia (modified to limit selection to patients with the required severity)
Meets at least one of the following ACOG criteria for severe preeclampsia (modified to limit selection to patients with the required severity)
. Proteinuria of 5 grams or higher in a 24-hour specimen or 3+ or greater on 2 random urine samples collected at least 4 hours apart
Has a fetal gestational age of 23 5/7 to 34 weeks.
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51 participants in 2 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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