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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 : April 6, 2023
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Study Description
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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.

Condition or disease
Systemic Lupus Erythematosus Antiphospholipid Syndrome

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 Design
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Study Type : Observational
Estimated Enrollment : 700 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
Study Start Date : September 2003
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lupus Pregnancy

Groups and Cohorts
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Group/Cohort
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Neonatal death [ Time Frame: Time of neonatal death ]
    Neonatal death prior to hospital discharge and due to complications of prematurity

  3. Preterm delivery prior to 36 weeks' gestation [ Time Frame: End of pregnancy ]
    Indicated preterm delivery prior to 36 weeks' gestation because of gestational hypertension, preeclampsia-eclampsia or placental insufficiency

  4. Small for gestational age (SGA) <5th %ile [ 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).


Secondary Outcome Measures :
  1. Gestational age [ Time Frame: End of pregnancy ]
    Gestational age (weeks and days) at the end of pregnancy

  2. Birth weight [ Time Frame: End of pregnancy ]
    Birth weight

  3. Number of days neonate requires positive pressure ventilation [ Time Frame: Neonate discharge from hospital ]
    Number of days neonate requires positive pressure ventilation

  4. Total number of days neonate is hospitalized [ Time Frame: Neonate discharge from hospital ]
    Total number of days neonate is hospitalized


Biospecimen Retention:   Samples With DNA
Serum, plasma, whole blood, RNA, urine

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Pregnant patients identified by investigators at each study site
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00198068


Contacts
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Contact: Marta M. Guerra, MS 212-774-7361 guerram@hss.edu

Locations
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United States, Illinois
Northwestern University Completed
Chicago, Illinois, United States, 60611
University of Chicago Completed
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins Hospital Completed
Baltimore, Maryland, United States, 21287
United States, New York
NYU Langone Medical Center/Hospital for Joint Diseases Recruiting
New York, New York, United States, 10016
Contact: Marta M Guerra, MS    212-774-7361    guerram@hss.edu   
Principal Investigator: Jill P. Buyon, M.D.         
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Marta M Guerra, MS    212-774-7361    guerram@hss.edu   
Principal Investigator: Michael D. Lockshin, M.D.         
Principal Investigator: Lisa R. Sammaritano, M.D.         
Columbia University Medical Center Completed
New York, New York, United States, 10032
United States, Oklahoma
Oklahoma Medical Research Foundation Completed
Oklahoma City, Oklahoma, United States, 73104
United States, Utah
University of Utah Salt Lake City Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Tyler R Cavin    801-585-7617    tyler.cavin@hsc.utah.edu   
Principal Investigator: Ware Branch, M.D.         
Principal Investigator: Flint Porter, M.D.         
Canada, Ontario
Mt. Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 2K4
Contact: Karen Spitzer    416-506-9203    kspitzer@triofertility.com   
Principal Investigator: Carl Laskin, M.D.         
United Kingdom
Guy's & St Thomas' NHS Foundation Trust Completed
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Hospital for Special Surgery, New York
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Jane E. Salmon, M.D. Hospital for Special Surgery, New York
More Information
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Additional Information:

Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT00198068    
Other Study ID Numbers: 2014-309
R01AR049772 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: April 6, 2023
Last Verified: April 2023
Individual Participant Data (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.
Keywords provided by Hospital for Special Surgery, New York:
Pregnancy outcomes
Systemic lupus erythematosus
Antiphospholipid syndrome
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Antiphospholipid Syndrome
Syndrome
Disease
 Pathologic Processes
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases