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Sponsors and Collaborators: |
Protherics GlaxoSmithKline |
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Information provided by: | Protherics |
ClinicalTrials.gov Identifier: | NCT00158743 |
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.
Condition | Intervention | Phase |
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Pre-Eclampsia |
Drug: Anti-digoxin antibody (FAB fragment) Drug: Digoxin Immune Fab ovine Drug: 0.9% sodium chloride |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study |
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 |
Enrollment: | 51 |
Study Start Date: | February 2004 |
Study Completion Date: | December 2007 |
Arms | Assigned Interventions |
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1: Active Comparator
Digibind treatment plus standard of care
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Drug: Anti-digoxin antibody (FAB fragment)
intravenous administered, dose based on weight (assuming 4ng/mL EDLF concentration). Dose every 6 hours x 48 hours.
Drug: 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
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2: Placebo Comparator
0.9% sodium chloride placebo (intravenous)plus standard of care
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Drug: 0.9% sodium chloride
normal saline placebo in equivalent volume to active comparator
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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.
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A subject with a diagnosis of severe preeclampsia will be eligible for inclusion if she meets the following criteria:
Meets both 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
Exclusion Criteria:
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 University |
Responsible Party: | Protherics ( Suzanne Ward ) |
Study ID Numbers: | DEEP |
Study First Received: | September 8, 2005 |
Last Updated: | December 18, 2007 |
ClinicalTrials.gov Identifier: | NCT00158743 |
Health Authority: | United States: Food and Drug Administration |
Pre-eclampsia Hypertension Endogenous digitalis-like factor Anti-digoxin antibody Digibind |
Immunoglobulin Fab Fragments Antibodies Hypertension, Pregnancy-Induced Pregnancy Complications Eclampsia Digoxin |
Pregnancy toxemia /hypertension Pre-Eclampsia Preeclampsia Immunoglobulins Hypertension |
Molecular Mechanisms of Pharmacological Action Immunologic Factors Cardiotonic Agents Therapeutic Uses Physiological Effects of Drugs |
Enzyme Inhibitors Anti-Arrhythmia Agents Cardiovascular Agents Protective Agents Pharmacologic Actions |