Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) (PROMISSE)

This study is currently recruiting participants.
Verified March 2014 by Hospital for Special Surgery, New York
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier:
NCT00198068
First received: September 12, 2005
Last updated: March 20, 2014
Last verified: March 2014

September 12, 2005
March 20, 2014
September 2003
August 2014   (final data collection date for primary outcome measure)
  • Otherwise unexplained fetal death occurring after 12 weeks gestation [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
    Fetal death occurring after 12 weeks' gestation and not explained by chromosomal abnormalities, anatomic malformations, or congenital infections.
  • Neonatal death prior to hospital discharge and due to complications of prematurity [ Time Frame: Time of neonatal death ] [ Designated as safety issue: No ]
  • Indicated preterm delivery prior to 36 weeks' gestation because of gestational hypertension, preeclampsia-eclampsia or placental insufficiency [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Small for gestational age (SGA) <5th %ile in the absence of anatomical or chromosomal abnormalities and/or delivery before 36 weeks because of intrauterine growth restriction (IUGR). [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00198068 on ClinicalTrials.gov Archive Site
  • Gestational age [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Birth weight [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  • Number of days neonate requires positive pressure ventilation [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]
  • Total number of days neonate is hospitalized [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)

The PROMISSE Study is an observational study of 700 pregnant patients, enrolled at nine major clinical centers. The purpose of the study is 1) to determine whether certain proteins (called complement split products) that can injure healthy organs can be used to predict poor pregnancy outcome in patients with systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS), and/or 2) to determine whether elevated levels of circulating antiangiogenic factors predict pregnancy complications in patients with aPL antibodies and/or SLE.

Thrombosis and pregnancy loss are common features of systemic lupus erythematosus (SLE), particularly in the presence of antiphospholipid (aPL) antibodies. The in vivo mechanisms by which aPL antibodies lead to vascular events and, specifically, to recurrent fetal loss are largely unknown. Studies in a mouse model of antiphospholipid antibody syndrome (APS) indicate that in vivo complement activation is necessary for fetal loss caused by aPL antibodies. This study represents an effort to translate these research observations on the potential role of complement activation in the pathogenesis of aPL antibody-mediated pregnancy loss to a clinically relevant human study.

In addition, studies in humans and mice have shown 1) that the balance of circulating angiogenic and antiangiogenic factors predicts preeclampsia and fetal growth restriction in healthy women, 2) circulating antiangiogenic factors cause endothelial dysfunction and abnormal placental development in animal models, and 3) complement activation leads to elevated levels of circulating antiangiogenic factors and complement inhibition prevents increased levels of antiangiogenic factors, placental dysfunction and fetal growth restriction in a mouse model of APS. This study will permit testing the hypothesis that, like in healthy women, the balance of circulating angiogenic and antiangiogenic factors predict complications in women with SLE and APS and to translate the findings in animal models into humans.

The PROMISSE Study is a prospective observational study that will follow 700 pregnant patients who will be grouped and analyzed according to the presence or absence of aPL antibodies and preexisting SLE. The patients are followed regularly during the course of the pregnancy, collecting medical and obstetrical information as well as serial blood specimens for complement and cytokine assays. The data obtained will be analyzed and used to identify mechanisms and predictors of poor fetal outcome. We expect that the insights provided through this study will suggest means to prevent, arrest or modify these conditions.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Serum, plasma, whole blood, RNA, urine

Non-Probability Sample

Pregnant patients identified by investigators at each study site

  • Systemic Lupus Erythematosus
  • Antiphospholipid Syndrome
Not Provided
  • Group 1: aPL+/SLE-
    Positive antiphospholipid antibodies (aPL) defined as positive LAC and/or anti cardiolipin IgG/IgM >= 40 units and/or anti-beta 2 glycoprotein I IgG or IgM >= 40 units; no SLE
  • Group 2: aPL+/SLE+
    Positive antiphospholipid antibodies (aPL) defined as positive LAC and/or anti cardiolipin IgG/IgM >= 40 units and/or anti-beta 2 glycoprotein I IgG or IgM >= 40 units AND SLE defined as four or more American College of Rheumatology criteria for SLE.
  • Group 3: aPL-/SLE+
    No antiphospholipid antibodies; SLE defined as four or more American College of Rheumatology criteria for SLE.
  • Group 4: aPL-/SLE-
    Healthy controls: no antiphospholipid antibodies; no SLE

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
700
August 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient pregnant with live intrauterine pregnancy, as defined by positive test for elevated β-HCG, but ≤ 12 weeks by gestation (for subjects without aPL antibodies) and ≤18 weeks (for subjects with aPL antibodies)
  • Patient between the ages of 18-45 and able to give informed consent, or age < 18 years with parental consent
  • Hematocrit > 26%
  • For APL positive:

    • aCL: IgG >= 40 GPL units; IgM >= 40 MPL units
    • Positive LAC (RVVT, Kaolin, dilute TTI or PTT LA)
    • Anti-β2GPI: IgG >= 40 GPL units; IgM >= 40 MPL units
  • For control subjects:

    • At least one successful pregnancy
    • No history of fetal death (death of conceptus ≥ 10 weeks' gestation)
    • No more than 1 miscarriage < 10 weeks' gestation
    • No history of positive aPL in local lab or positive aPL in core labs at screening
    • Not currently a smoker
    • No medical problems requiring chronic treatment

Exclusion Criteria:

  • Diabetes mellitus (Type I and Type II) antedating pregnancy
  • Multiple fetal gestations
  • Known or suspected hereditary complement deficiency (defined by CH50 = 0)
Female
18 Years to 45 Years
Yes
Contact: Marta M. Guerra, MS 212-774-7361 guerram@hss.edu
Contact: Aanam Aslam, AB 212-7742115 aslama@hss.edu
United States,   Canada,   United Kingdom
 
NCT00198068
22122, R01AR049772
Yes
Hospital for Special Surgery, New York
Hospital for Special Surgery, New York
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Jane E. Salmon, M.D. Hospital for Special Surgery, New York
Hospital for Special Surgery, New York
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP