Pharmacokinetics, Safety and Efficacy Study of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia



Status:Active, not recruiting
Conditions:Women's Studies
Therapuetic Areas:Reproductive
Healthy:No
Age Range:16 - Any
Updated:4/21/2016
Start Date:May 2014
End Date:November 2016

Use our guide to learn which trials are right for you!

Prospective Randomized Double-Blind, Placebo Controlled Evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia (PRESERVE-1)

The purpose of the study is to assess the efficacy, safety and pharmacokinetics (PK) of
recombinant human antithrombin (ATryn) in addition to expectant management for the treatment
of preterm preeclampsia (PPE). Efficacy will be assessed by comparing the difference in
extension of gestational age from the time of randomization into the study until delivery
between ATryn and placebo treated subjects. In addition, the effect of ATryn on fetal and
neonatal clinical outcomes will be assessed. The PK characteristics of ATryn in the subjects
will be investigated by measuring AT activity levels in the mother during treatment and in
cord blood.

Hospitalized PPE patients who are being expectantly managed, after initial assessment and
stabilization period, will be considered for the study. After informed consent has been
obtained subjects will be screened for eligibility. Screening includes obtaining the
subject's medical/obstetric history and a physical examination which includes an assessment
of maternal and fetal status. Blood samples for hematology, clinical chemistries,
biomarkers, coagulation, immunogenicity and AT activity levels will be drawn. Urine will be
collected for baseline urinalysis, protein/creatinine ratio and biomarkers. Eligible
subjects who meet inclusion/exclusion criteria will be randomized in a 1:1 ratio to receive
a continuous infusion of either ATryn or placebo.

Sampling for AT activity will be performed immediately prior to the first dose of study drug
and at specified times thereafter.

Subjects will continue on study drug until maternal and/or fetal indications for delivery
necessitate cessation of expectant management or until 34 0/7 weeks of gestation. The
average extension of pregnancy with standard of care expectant management in this patient
population is approximately 7 days. It is assumed that treatment with ATryn will provide an
additional increase in gestational age of 5-7 days as compared to this standard of care.
Total duration on study drug is therefore estimated to be approximately 7 to 14 days on
average.

Post treatment assessments of the mother will be performed at hospital discharge and
approximately 4-6 weeks after delivery of the neonate. Information on the neonates will be
collected until they reach a post-menstrual age (PMA) of 36 weeks. If the neonate reaches 36
weeks PMA < 28 days following delivery, the final neonatal follow-up visit should be done at
the 4-6 week post-delivery visit.

Inclusion Criteria:

1. Hospitalized female pregnant patients of gestational age of ≥23 0/7 weeks to ≤30 0/7
weeks (for subjects at gestational age 23 0/7 to 23 6/7 all standard interventions
including antenatal steroids and cesarean for fetal indications must be offered).

Gestational age determination by local practice using one of the following three
approaches:

- Last menstrual period (LMP) dating and confirmatory ultrasound

- Ultrasound alone when LMP is not reliable

- Known date of conception in the setting of assisted reproductive technology

2. At least 16 years of age (NOTE: different age restrictions may apply per local
regulation and/or ethical considerations; subjects under the local age of consent may
be excluded at the discretion of the reviewing IRB/IEC)

3. Recent diagnosis of Preeclampsia or Superimposed Preeclampsia as defined by:

• For Preeclampsia

- Gestational hypertension defined as a recorded systolic blood pressure (BP) of

≥140 mm Hg or diastolic BP of ≥90 mm Hg on 2 occasions at least 4 hours apart
(since the commencement of medical intervention in any facility) OR

- Severe gestational hypertension defined as systolic blood pressure of ≥ 160 mm
Hg or diastolic blood pressure ≥ 110 mm Hg, confirmed with second assessment
within a short interval (minutes) AND

- New onset of any of the following:

- Proteinuria defined as ≥0.3 g protein per 24 hours in a 12-24 hour urine
collection or protein/creatinine ratio of ≥0.3 mg/mg* (on a random sample
or any collection period.)

- Platelet count less than 100,000/μL

- Serum creatinine concentrations greater than 1.1 mg/dL in the absence of
other renal disease

- Elevated liver transaminases to ≥ twice upper limit of normal

- Cerebral or visual symptoms

For Superimposed preeclampsia:

- The start of antihypertensive medication, increasing the dose of a currently
administered antihypertensive medication or adding a second antihypertensive
medication after 20 weeks of pregnancy for systolic BP ≥ 160 or diastolic BP ≥
105 in a patient that had a previous history of controlled hypertension before
20 weeks of pregnancy. AND

- New onset of any of the following:

- proteinuria defined as ≥0.3 g protein per 24 hours in a 12-24 hour urine
collection or protein/creatinine ratio of ≥0.3 mg/mg (on a random sample or
any collection period)

- Platelet count less than 100,000/μL

- Serum creatinine concentrations greater than 1.1 mg/dL in the absence of
other renal disease

- Elevated liver transaminases to ≥ twice upper limit of normal

- Cerebral or visual symptoms

4. In the opinion of the investigator the patient has demonstrated sufficient clinical
stability to be eligible for expectant management

5. The patient is expected to be managed as an inpatient until delivery

6. Signed informed consent for both subject and neonate

Exclusion Criteria:

1. Criteria that would likely require immediate delivery of the fetus are exclusionary
if present just prior to randomization:

- Refractory hypertension despite maximal medical intervention of systolic BP ≥160
mm Hg or diastolic BP of ≥110 mm Hg

- Thrombocytopenia (platelets ˂ 100/mm3) with or without Hemolysis elevated liver
enzymes low platelets (HELLP) syndrome defined as defined as Aspartate amino
transferase (AST) ≥70 units/L, and platelets ˂100/mm3, and evidence of hemolysis
on blood film plus either Lactic dehydrogenase (LDH) ≥600 IU/mL or total
bilirubin ≥1.2 mg/dL)

- Oliguria (≤500 mL/24 hours) or evidence of progressive renal insufficiency

- Serum creatinine concentration greater than 1.1 mg/dL

- Persistent visual disturbances

- Placental abruption

- Pulmonary edema

- Nonreassuring fetal heart rate tracing

- Intractable headache unrelieved with analgesia

- Intractable right upper quadrant abdominal pain or vomiting

- If umbilical Doppler ultrasound has been performed, the presence of an abnormal
umbilical artery Doppler as defined by absent or reverse end diastolic flow

- Biophysical score ≤ 4/10 on 2 occasions

- Oligohydramnios (deepest vertical pocket less than 2 x 2cm on ultrasound)

- Other maternal or fetal conditions that would preclude expectant management

2. Known lethal or major fetal anomaly

3. Recent (within 12 months) history of maternal alcoholism or drug dependence

4. Diagnosis of epilepsy

5. Has need for chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs)
including selective cyclooxygenase (Cox)-2 inhibitors, or unwilling to abstain from
use of NSAIDs during the study treatment period (low dose aspirin of 81 mg/day or
less allowable)

6. Received within 72 hours or has requirement for heparin; low molecular weight
heparins such as enoxaparin or dalteparin; fondaparinux; antiplatelet agents such as
clopidogrel, prasugrel, or high dose aspirin (>81 mg/day); Direct Thrombin Inhibitors
(DTI) such as dabigatran

7. Pre-existing renal disease, documented pre-pregnancy or in pregnancy prior to 20
weeks gestation (prior to the diagnosis of preeclampsia) or 24 hr urine of ≥0.3 gm/24
hours, documented in pregnancy, prior to 20 weeks gestation or ≥2+ dipstick or ≥ 0.3
PCR, documented in pregnancy at the last available test prior to 20 weeks gestation.
In the case of conflicting results between dipstick, PCR, and timed urine collection
tests to work up an episode of proteinuria, the timed urine collection result would
supersede other results

8. Multi-fetal pregnancy

9. History of Antiphospholipid antibody syndrome

10. Known hypersensitivity to goat and goat milk proteins

11. Participation in another interventional clinical trial of an investigational,
unapproved therapy (drug, biologic, device) within 30 days of consent
We found this trial at
29
sites
630 W 168th St
New York, New York
212-305-2862
Principal Investigator: Kirsten Cleary, MD
Phone: 917-686-0653
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
?
mi
from
New York, NY
Click here to add this to my saved trials
5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: Sarosh Rana, MD
Phone: 773-702-5159
University of Chicago One of the world's premier academic and research institutions, the University of...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
234 Goodman Dr
Cincinnati, Ohio 45229
(513) 584-1000
Principal Investigator: Emily DeFranco, MD
University of Cincinnati Medical Center Opening in 1823 as the country
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Durham, North Carolina 27710
(919) 684-8111
Principal Investigator: Chad Grotegut, MD
Phone: 919-681-0308
Duke University Younger than most other prestigious U.S. research universities, Duke University consistently ranks among...
?
mi
from
Durham, NC
Click here to add this to my saved trials
301 University Blvd
Galveston, Texas 77555
(409) 772-1011
Principal Investigator: George Saade, MD
Phone: 409-772-0991
University of Texas Medical Branch Established in 1891 as the University of Texas Medical Department,...
?
mi
from
Galveston, TX
Click here to add this to my saved trials
1200 Moursund Street
Houston, Texas 77030
(713) 798-4951
Principal Investigator: Manisha Ghandi, MD
Phone: 832-824-0403
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
?
mi
from
Houston, TX
Click here to add this to my saved trials
2500 N State St
Jackson, Mississippi 39216
(601) 984-1000
Principal Investigator: Sarah Novotny, MD
Phone: 601-984-5377
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
?
mi
from
Jackson, MS
Click here to add this to my saved trials
Little Rock, Arkansas 72202
Principal Investigator: Everett Magann, MD
Phone: 501-686-8345
?
mi
from
Little Rock, AR
Click here to add this to my saved trials
Norfolk, Virginia 23507
Principal Investigator: James Hill, MD
Phone: 757-446-0529
?
mi
from
Norfolk, VA
Click here to add this to my saved trials
4202 E Fowler Ave
Tampa, Florida 33620
(813) 974-2011
Principal Investigator: Judette Louis, MD
Phone: 813-259-8680
University of South Florida The University of South Florida is a high-impact, global research university...
?
mi
from
Tampa, FL
Click here to add this to my saved trials
1200 S Cedar Crest Blvd
Allentown, Pennsylvania 18103
(610) 402-8000
Principal Investigator: John Smulian, MD
Lehigh Valley Hospital At Lehigh Valley Health Network, we continually go the extra mile to...
?
mi
from
Allentown, PA
Click here to add this to my saved trials
Birmingham, Alabama 35294
Principal Investigator: Alan Tita, MD
Phone: 205-934-5509
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Chattanooga, Tennessee 37403
Principal Investigator: Garrett Lam, MD
Phone: 423-664-4460
?
mi
from
Chattanooga, TN
Click here to add this to my saved trials
303 East Superior Street
Chicago, Illinois 60611
Principal Investigator: William Grobman, MD
Phone: 312-503-3200
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Cincinnati, Ohio 45211
Principal Investigator: Mounira Habli, MD
Phone: 513-862-2707
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
22101 Moross Rd
Detroit, Michigan 48236
(313) 343-4000
Principal Investigator: Mitchell Dombrowski, MD
Phone: 313-268-8914
Saint John Hospital and Medical Center Founded in 1952, St. John Hospital and Medical Center...
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Baha Sibai, MD
Phone: 713-500-5850
?
mi
from
Houston, TX
Click here to add this to my saved trials
Louisville, Kentucky 40207
Principal Investigator: Helen How, MD
Phone: 502-629-2433
?
mi
from
Louisville, KY
Click here to add this to my saved trials
307 N University Blvd
Mobile, Alabama 36688
(251) 460-6101
Principal Investigator: David Lewis, MD
Phone: 251-415-1598
University of South Alabama "University of South Alabama is a public institution that was founded...
?
mi
from
Mobile, AL
Click here to add this to my saved trials
Murray, Utah 84107
Principal Investigator: Dr. Branch, MD
Phone: 801-507-7036
?
mi
from
Murray, UT
Click here to add this to my saved trials
20 York St, N20 York St,
New Haven, Connecticut 06520
(203) 688-4242
Principal Investigator: Michael Paidas, MD
Phone: 203-737-1982
Yale-New Haven Hospital Relying on the skill and expertise of more than 4,500 university and...
?
mi
from
New Haven, CT
Click here to add this to my saved trials
New Orleans, Louisiana 70112
Principal Investigator: Sherri Longo, MD
Phone: 504-894-3039
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
940 NE 13th St
Oklahoma City, Oklahoma 73190
(405) 271-6458
Principal Investigator: Christina M Scifres, MD
Phone: 405-271-5597
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
?
mi
from
Oklahoma City, OK
Click here to add this to my saved trials
Orange, California 92868
Principal Investigator: Deborah Wing, MD
Phone: 714-456-2217
?
mi
from
Orange, CA
Click here to add this to my saved trials
Providence, Rhode Island 02905
Principal Investigator: Erika Werner, MD
Phone: 401-274-1122
?
mi
from
Providence, RI
Click here to add this to my saved trials
Saint Louis, Missouri 63130
Principal Investigator: Erol Amon, MD
Phone: 314-977-2090
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
Salt Lake City, Utah 84132
Principal Investigator: Robert Silver, MD
Phone: 801-585-6996
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
San Fransisco, California 94122
Principal Investigator: Mari-Paule Thiet, MD
Phone: 415-502-0131
?
mi
from
San Fransisco, CA
Click here to add this to my saved trials
1 Barnes Jewish Hospital Plaza
St. Louis, Missouri 63110
(314) 747-3000
Principal Investigator: George Macones, MD
Phone: 314-362-8523
Barnes Jewish Hospital Barnes-Jewish Hospital at Washington University Medical Center is the largest hospital in...
?
mi
from
St. Louis, MO
Click here to add this to my saved trials