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

April 5, 2024 updated by: Hospital for Special Surgery, New York
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.

Study Overview

Status

Recruiting

Conditions

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

Enrollment (Estimated)

700

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Marta M. Guerra, MS
  • Phone Number: 212-774-7361
  • Email: guerram@hss.edu

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2K4
        • Recruiting
        • Mt. Sinai Hospital
        • Contact:
        • Principal Investigator:
          • Carl Laskin, M.D.
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Completed
        • Guy's & St Thomas' NHS Foundation Trust
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Completed
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Completed
        • Northwestern University
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Completed
        • Johns Hopkins Hospital
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Hospital For Special Surgery
        • Contact:
        • Principal Investigator:
          • Michael D. Lockshin, M.D.
        • Principal Investigator:
          • Lisa R. Sammaritano, M.D.
      • New York, New York, United States, 10032
        • Completed
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • Recruiting
        • NYU Langone Medical Center/Hospital for Joint Diseases
        • Contact:
        • Principal Investigator:
          • Jill P. Buyon, M.D.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Completed
        • Oklahoma Medical Research Foundation
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah Salt Lake City
        • Contact:
        • Principal Investigator:
          • Ware Branch, M.D.
        • Principal Investigator:
          • Flint Porter, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Pregnant patients identified by investigators at each study site

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
End of pregnancy
Neonatal death
Time Frame: Time of neonatal death
Neonatal death prior to hospital discharge and due to complications of prematurity
Time of neonatal death
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
End of pregnancy
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).
End of pregnancy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gestational age
Time Frame: End of pregnancy
Gestational age (weeks and days) at the end of pregnancy
End of pregnancy
Birth weight
Time Frame: End of pregnancy
Birth weight
End of pregnancy
Number of days neonate requires positive pressure ventilation
Time Frame: Neonate discharge from hospital
Number of days neonate requires positive pressure ventilation
Neonate discharge from hospital
Total number of days neonate is hospitalized
Time Frame: Neonate discharge from hospital
Total number of days neonate is hospitalized
Neonate discharge from hospital

Collaborators and Investigators

This is where you will find people and organizations involved with this 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimated)

September 20, 2005

Study Record Updates

Last Update Posted (Actual)

April 8, 2024

Last Update Submitted That Met QC Criteria

April 5, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-309
  • R01AR049772 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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