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

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ClinicalTrials.gov Identifier: NCT00198068
Recruitment Status : Recruiting
First Posted : September 20, 2005
Last Update Posted : October 28, 2019
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Tracking Information
First Submitted Date September 12, 2005
First Posted Date September 20, 2005
Last Update Posted Date October 28, 2019
Study Start Date September 2003
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 22, 2011)
  • Otherwise unexplained fetal death occurring after 12 weeks gestation [ Time Frame: End of pregnancy ]
    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 ]
  • Indicated preterm delivery prior to 36 weeks' gestation because of gestational hypertension, preeclampsia-eclampsia or placental insufficiency [ Time Frame: End of pregnancy ]
  • 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 ]
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00198068 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: December 26, 2007)
  • Gestational age [ Time Frame: End of pregnancy ]
  • Birth weight [ Time Frame: End of pregnancy ]
  • Number of days neonate requires positive pressure ventilation [ Time Frame: Neonate discharge from hospital ]
  • Total number of days neonate is hospitalized [ Time Frame: Neonate discharge from hospital ]
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Official Title Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Brief Summary 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.
Detailed Description

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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum, plasma, whole blood, RNA, urine
Sampling Method Non-Probability Sample
Study Population Pregnant patients identified by investigators at each study site
Condition
  • Systemic Lupus Erythematosus
  • Antiphospholipid Syndrome
Intervention Not Provided
Study Groups/Cohorts
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 6, 2009)
700
Original Enrollment
 (submitted: September 12, 2005)
400
Estimated Study Completion Date August 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
  • Known or suspected hereditary complement deficiency (defined by CH50 = 0)
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Marta M. Guerra, MS 212-774-7361 guerram@hss.edu
Listed Location Countries Canada,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00198068
Other Study ID Numbers 2014-309
R01AR049772 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: Because the investigative team is still analyzing the data for biomarkers and genetics, the authors are not willing to make the data public at this time. Published study results can be found under Publications on the ClinicalTrials.gov site for this study.
Responsible Party Hospital for Special Surgery, New York
Study Sponsor Hospital for Special Surgery, New York
Collaborators National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Principal Investigator: Jane E. Salmon, M.D. Hospital for Special Surgery, New York
PRS Account Hospital for Special Surgery, New York
Verification Date October 2019