Efficacy Study of Digibind for Treatment of Severe Preeclampsia

NCT00158743 | Completed Phase 2 Results DMC

• 1 other identifier: DEEP
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Pre-eclampsia

Keywords

Pre-eclampsia; Hypertension; Endogenous digitalis-like factor; Anti-digoxin antibody; Digibind

Outcome Measures

Primary Outcomes (1)

• Change in Creatinine Clearance

  change from baseline in creatinine clearance measured at 24 to 48 hours, comparing patients who received placebo with those who received digoxin immune fab

  Baseline to 24-48 hours.

Study Arms (2)

Digoxin immune fab

ACTIVE COMPARATOR

Digibind treatment plus standard of care

Drug: Anti-digoxin antibody (FAB fragment)

placebo (sodium chloride)

PLACEBO COMPARATOR

Other: sodium chloride

Interventions

Anti-digoxin antibody (FAB fragment) DRUG

intravenous administered, dose based on weight (assuming 4ng/mL EDLF concentration). Dose every 6 hours x 48 hours.

Also known as: Digibind

Digoxin immune fab

sodium chloride OTHER

placebo (sodium chloride)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• A systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher occurring after 20 weeks of gestation in a woman whose blood pressure has previously been normal;
• Proteinuria, with excretion of 0.3 g or more of protein in a 24-hour urine specimen or a urine dipstick reading of 1+ or more.
• 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
• A systolic blood pressure of 160 mm Hg or higher or a diastolic blood pressure of 110 mm Hg or higher on two occasions six or more hours apart in a pregnant woman who is on bed rest;
• Oliguria, with excretion of less than 500 ml of urine in 24 hours or average of ≤ 25 ml/hour over a 3 hour period;
• Pulmonary edema;
• Impairment of liver function \[AST(SGOT) \> 72 U/L or ALT(SGPT) \> 72 U/L or LDH \> 600 U/L or Total Bilirubin \>1.2 mg/DL)\];
• Visual or cerebral disturbances;
• Decreased platelet count (≥50,000/mm3 and ≤ 100,000/mm3).
• Has a fetal gestational age of 23 5/7 to 34 weeks.

You may not qualify if:

• Is in need of immediate delivery as soon as clinically appropriate
• Eclampsia
• Significant antecedent obstetrical problems which may interfere with study assessments or safe participation in the study
• Evidence of non-reassuring fetal well being
• Evidence of lethal fetal anomaly
• Antecedent hypertension (hypertension secondary to preeclampsia, treated or untreated is allowed)
• Antecedent renal, hepatic, or autoimmune disease
• Medical or psychiatric disorder which is unstable or which might interfere with study assessments or safe participation in the study
• Evidence on medical history/evaluation of use of or need for digitalis-like products currently or in the future
• History of a severe allergic reaction to previous medication, severe asthma, or atopy. (Patients with a history of allergic reactions to antibiotics, papain, chymopapain, or other papaya extracts may be more susceptible to allergic reactions to Digibind®)
• Prior use of antibodies/FAB fragments from sheep (e.g. Digibind®, DigiFab, CroFab)
• Serum creatinine ≥ 1.5 mg/dl
• Platelet count \<50,000/mm3
• Patient intends to breast feed and does not agree to wait for a minimum of seven days after the last Digibind® dose (a breast pump would be used for this seven day period)
• Inability to understand and provide informed consent

Sponsors & Collaborators

• BTG International Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (8)

University of South Alabama

Mobile, Alabama, 36604, United States

Location

Phoenix Perinatal Associates

Phoenix, Arizona, 85014, United States

Location

Winnie Palmer Hospital

Orlando, Florida, 32806, United States

Location

Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, PO Box 33932, 1501 Kings Highway

Shreveport, Louisiana, 71130, United States

Location

St Mary's Health Center

St Louis, Missouri, 63117, United States

Location

Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 634, PO Box 250619

Charleston, South Carolina, 29425, United States

Location

Department of OB-GYN, Division of Maternal Fetal Medicine, University of Texas Medical Branch, 301 University Boulevard

Galveston, Texas, 77555-0587, United States

Location

St Mark's Hospital

Salt Lake City, Utah, 84124, United States

Location

Related Publications (8)

• Adair CD, Buckalew V, Taylor K, Ernest JM, Frye AH, Evans C, Veille JC. Elevated endoxin-like factor complicating a multifetal second trimester pregnancy: treatment with digoxin-binding immunoglobulin. Am J Nephrol. 1996;16(6):529-31. doi: 10.1159/000169054.

  PMID: 8955766 BACKGROUND

• Gusdon JP Jr, Buckalew VM Jr, Hennessy JF. A digoxin-like immunoreactive substance in preeclampsia. Am J Obstet Gynecol. 1984 Sep 1;150(1):83-5. doi: 10.1016/s0002-9378(84)80114-3.

  PMID: 6540989 BACKGROUND

• Poston L, Morris JF, Wolfe CD, Hilton PJ. Serum digoxin-like substances in pregnancy-induced hypertension. Clin Sci (Lond). 1989 Aug;77(2):189-94. doi: 10.1042/cs0770189.

  PMID: 2548800 BACKGROUND

• Graves SW, Williams GH. An endogenous ouabain-like factor associated with hypertensive pregnant women. J Clin Endocrinol Metab. 1984 Dec;59(6):1070-4. doi: 10.1210/jcem-59-6-1070.

  PMID: 6092405 BACKGROUND

• Lopatin DA, Ailamazian EK, Dmitrieva RI, Shpen VM, Fedorova OV, Doris PA, Bagrov AY. Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia. J Hypertens. 1999 Aug;17(8):1179-87. doi: 10.1097/00004872-199917080-00018.

  PMID: 10466474 BACKGROUND

• Krep H, Price DA, Soszynski P, Tao QF, Graves SW, Hollenberg NK. Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats. Am J Hypertens. 1995 Sep;8(9):921-7. doi: 10.1016/0895-7061(95)00181-N.

  PMID: 8541008 BACKGROUND

• Krep HH, Graves SW, Price DA, Lazarus M, Ensign A, Soszynski PA, Hollenberg NK. Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications. Am J Hypertens. 1996 Jan;9(1):39-46. doi: 10.1016/0895-7061(95)00260-x.

  PMID: 8834705 BACKGROUND

• Gruber KA, Whitaker JM, Buckalew VM Jr. Endogenous digitalis-like substance in plasma of volume-expanded dogs. Nature. 1980 Oct 23;287(5784):743-5. doi: 10.1038/287743a0. No abstract available.

  PMID: 6253813 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia; Hypertension

Interventions

Immunoglobulin Fab Fragments; digoxin antibodies Fab fragments; Sodium Chloride

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Suzanne Ward Pharm D
• Organization: BTG International Inc

suzanne.ward@btgplc.com

610-278-1660

Study Officials

• Vardaman M Buckalew, MD

  Wake Forest University Health Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: February 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: August 8, 2014
• Results First Posted: August 8, 2014

Record last verified: 2014-07

Locations

US (8)