Efficacy Study of Digibind for Treatment of Severe Preeclampsia
Condition: Pre-eclampsia
MeSH terms: Pre-Eclampsia; Eclampsia
Intervention: Anti-digoxin antibody (FAB fragment); sodium chloride
Intervention description: intravenous administered, dose based on weight (assuming 4ng/mL EDLF concentration). Dose every 6 hours x 48 hours.
Intervention MeSH terms: Digoxin; Antibodies; Immunoglobulin Fab Fragments
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 51.0
Sex: Female
Healthy volunteers: No
Keywords: Pre-eclampsia; Hypertension; Endogenous digitalis-like factor; Anti-digoxin antibody; Digibind

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A subject with a diagnosis of severe preeclampsia will be eligible for inclusion if
             she meets the following criteria:

               1. 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.

               2. 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.

               3. 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).

               4. Has a fetal gestational age of 23 5/7 to 34 weeks.

        Exclusion Criteria:

          1. Is in need of immediate delivery as soon as clinically appropriate

          2. Eclampsia

          3. Significant antecedent obstetrical problems which may interfere with study assessments
             or safe participation in the study

          4. Evidence of non-reassuring fetal well being

          5. Evidence of lethal fetal anomaly

          6. Antecedent hypertension (hypertension secondary to preeclampsia, treated or untreated
             is allowed)

          7. Antecedent renal, hepatic, or autoimmune disease

          8. Medical or psychiatric disorder which is unstable or which might interfere with study
             assessments or safe participation in the study

          9. Evidence on medical history/evaluation of use of or need for digitalis-like products
             currently or in the future

         10. 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®)

         11. Prior use of antibodies/FAB fragments from sheep (e.g. Digibind®, DigiFab, CroFab)

         12. Serum creatinine ≥ 1.5 mg/dl

         13. Platelet count <50,000/mm3

         14. 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)

         15. Inability to understand and provide informed consent