Efficacy Study of Digibind for Treatment of Severe Preeclampsia
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.
Drug: Anti-digoxin antibody (FAB fragment)
Drug: Digoxin Immune Fab ovine
Drug: 0.9% sodium chloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Parallel, Double-Blind, Placebo Controlled, Randomized Comparison of an Anti-Digoxin Antibody (Digibind) Versus Placebo for the Treatment of Antepartum Patients With Severe Preeclampsia|
- Proportion of patients during the treatment phase requiring: initiation of antihypertensive treatment;or
- in the case of patients entering the study already on an antihypertensive, requiring an increase in the dose or initiation of a secondary antihypertensive; or
- requiring delivery due to failure to control hypertension.
- Change in creatinine clearance from screening period.
- Clinical Global Impressions (CGI) - Improvement* (see below)
- Responder analysis (Proportion of responders at the end of the treatment period. A responder is defined as a patient rated much or very much improved on the CGI-I scale.)
- Improvement scores across time.
- Change from baseline in Clinical Global Impressions - Severity score at time points of interest.
- Delivery latency from diagnosis and from first dose of study medication.
- Proportion of patients completing the 48-hour treatment phase.
- Change from baseline in: blood pressure,edema,renal and hepatic function parameters.
- Proportion of patients with hemolysis.
- Change from baseline in platelet count.
- Change from baseline in Doppler assessed blood flow in the fetal umbilical and middle cerebral arteries.
- Proportion of patients experiencing adverse events.
- *Clinical Global Impression-Improvement Scale
- Considering your total clinical experience with this
- patient population, how ill is the patient at this
- time? (Normal, not ill at all; Borderline ill; Mildly ill; Moderately ill; Markedly ill; Severely ill; Among the most extremely ill patients
- Compared to her condition at admission to
- the study, how much has she changed? (Very much improved; Much improved; Minimally improved; No change; Minimally worse; Much worse; Very much worse)
|Study Start Date:||February 2004|
|Study Completion Date:||December 2007|
Active Comparator: 1
Digibind treatment plus standard of care
Drug: Anti-digoxin antibody (FAB fragment)
intravenous administered, dose based on weight (assuming 4ng/mL EDLF concentration). Dose every 6 hours x 48 hours.
Other Name: DigibindDrug: Digoxin Immune Fab ovine
Dosing is a calculated amount based on weight of patient #vials = (4 x weight in kg)/(100) and assumption of EDLF concentration of 4 ng/mL
Other Name: Digibind
Placebo Comparator: 2
0.9% sodium chloride placebo (intravenous)plus standard of care
Drug: 0.9% sodium chloride
normal saline placebo in equivalent volume to active comparator
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.
|United States, Alabama|
|University of South Alabama|
|Mobile, Alabama, United States, 36604|
|United States, Arizona|
|Phoenix Perinatal Associates|
|Phoenix, Arizona, United States, 85014|
|United States, Florida|
|Winnie Palmer Hospital|
|Orlando, Florida, United States, 32806|
|United States, Louisiana|
|Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, PO Box 33932, 1501 Kings Highway|
|Shreveport, Louisiana, United States, 71130|
|United States, Missouri|
|St Mary's Health Center|
|St Louis, Missouri, United States, 63117|
|United States, South Carolina|
|Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 634, PO Box 250619|
|Charleston, South Carolina, United States, 29425|
|United States, Texas|
|Department of OB-GYN, Division of Maternal Fetal Medicine, University of Texas Medical Branch, 301 University Boulevard|
|Galveston, Texas, United States, 77555-0587|
|United States, Utah|
|St Mark's Hospital|
|Salt Lake City, Utah, United States, 84124|
|Study Chair:||Vardaman M Buckalew, MD||Wake Forest School of Medicine|