NCT00198068

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
700

participants targeted

Target at P75+ for all trials

Timeline
9mo left

Started Sep 2003

Longer than P75 for all trials

Geographic Reach
3 countries

10 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress97%
Sep 2003Mar 2027

Study Start

First participant enrolled

September 1, 2003

Completed
2 years until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 20, 2005

Completed
21.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

April 28, 2026

Status Verified

March 1, 2026

Enrollment Period

23.5 years

First QC Date

September 12, 2005

Last Update Submit

April 23, 2026

Conditions

Systemic Lupus ErythematosusAntiphospholipid Syndrome

Keywords

Pregnancy outcomesSystemic lupus erythematosusAntiphospholipid syndrome

Outcome Measures

Primary Outcomes (4)

  • Otherwise unexplained fetal death occurring after 12 weeks gestation

    Fetal death occurring after 12 weeks' gestation and not explained by chromosomal abnormalities, anatomic malformations, or congenital infections.

    End of pregnancy

  • 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

    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

    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 Outcomes (4)

  • Gestational age

    End of pregnancy

  • Birth weight

    End of pregnancy

  • Number of days neonate requires positive pressure ventilation

    Neonate discharge from hospital

  • Total number of days neonate is hospitalized

    Neonate discharge from hospital

Study Arms (4)

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

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Pregnant patients identified by investigators at each study site

You may qualify if:

  • 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

You may not qualify if:

  • Diabetes mellitus (Type I and Type II) antedating pregnancy
  • Known or suspected hereditary complement deficiency (defined by CH50 = 0)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Northwestern University

Chicago, Illinois, 60611, United States

COMPLETED

University of Chicago

Chicago, Illinois, 60637, United States

COMPLETED

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

COMPLETED

NYU Langone Medical Center/Hospital for Joint Diseases

New York, New York, 10016, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

COMPLETED

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

COMPLETED

University of Utah Salt Lake City

Salt Lake City, Utah, 84132, United States

RECRUITING

Mt. Sinai Hospital

Toronto, Ontario, M5G 2K4, Canada

RECRUITING

Guy's & St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

COMPLETED

Related Publications (17)

  • Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med. 2004 Nov;10(11):1222-6. doi: 10.1038/nm1121. Epub 2004 Oct 17.

    PMID: 15489858BACKGROUND

  • Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA, Lambris JD, Holers VM, Salmon JE. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest. 2003 Dec;112(11):1644-54. doi: 10.1172/JCI18817. Erratum In: J Clin Invest. 2004 Feb;113(4):646.

    PMID: 14660741BACKGROUND

  • Holers VM, Girardi G, Mo L, Guthridge JM, Molina H, Pierangeli SS, Espinola R, Xiaowei LE, Mao D, Vialpando CG, Salmon JE. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med. 2002 Jan 21;195(2):211-20. doi: 10.1084/jem.200116116.

    PMID: 11805148BACKGROUND

  • Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012 Jul;64(7):2311-8. doi: 10.1002/art.34402.

    PMID: 22275304RESULT

  • Buyon JP, Kim MY, Guerra MM, Laskin CA, Petri M, Lockshin MD, Sammaritano L, Branch DW, Porter TF, Sawitzke A, Merrill JT, Stephenson MD, Cohn E, Garabet L, Salmon JE. Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study. Ann Intern Med. 2015 Aug 4;163(3):153-63. doi: 10.7326/M14-2235.

    PMID: 26098843RESULT

  • Kim MY, Buyon JP, Guerra MM, Rana S, Zhang D, Laskin CA, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Porter TF, Merrill JT, Stephenson MD, Gao Q, Karumanchi SA, Salmon JE. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol. 2016 Jan;214(1):108.e1-108.e14. doi: 10.1016/j.ajog.2015.09.066. Epub 2015 Sep 29.

    PMID: 26432463RESULT

  • Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, Lockshin MD, Petri M, Merrill JT, Sammaritano LR, Kim MY, Salmon JE. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016 Jan 12;3(1):e000131. doi: 10.1136/lupus-2015-000131. eCollection 2016.

    PMID: 26835148RESULT

  • Yelnik CM, Porter TF, Branch DW, Laskin CA, Merrill JT, Guerra MM, Lockshin MD, Buyon JP, Petri M, Sammaritano LR, Stephenson MD, Kim MY, Salmon JE. Brief Report: Changes in Antiphospholipid Antibody Titers During Pregnancy: Effects on Pregnancy Outcomes. Arthritis Rheumatol. 2016 Aug;68(8):1964-9. doi: 10.1002/art.39668.

    PMID: 26990620RESULT

  • Buyon JP, Kim MY, Guerra MM, Lu S, Reeves E, Petri M, Laskin CA, Lockshin MD, Sammaritano LR, Branch DW, Porter TF, Sawitzke A, Merrill JT, Stephenson MD, Cohn E, Salmon JE. Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic Cohort of Pregnant Patients with Lupus. Clin J Am Soc Nephrol. 2017 Jun 7;12(6):940-946. doi: 10.2215/CJN.11431116. Epub 2017 Apr 11.

    PMID: 28400421RESULT

  • Kim MY, Guerra MM, Kaplowitz E, Laskin CA, Petri M, Branch DW, Lockshin MD, Sammaritano LR, Merrill JT, Porter TF, Sawitzke A, Lynch AM, Buyon JP, Salmon JE. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis. 2018 Apr;77(4):549-555. doi: 10.1136/annrheumdis-2017-212224. Epub 2018 Jan 25.

    PMID: 29371202RESULT

  • Hong S, Banchereau R, Maslow BL, Guerra MM, Cardenas J, Baisch J, Branch DW, Porter TF, Sawitzke A, Laskin CA, Buyon JP, Merrill J, Sammaritano LR, Petri M, Gatewood E, Cepika AM, Ohouo M, Obermoser G, Anguiano E, Kim TW, Nulsen J, Nehar-Belaid D, Blankenship D, Turner J, Banchereau J, Salmon JE, Pascual V. Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy. J Exp Med. 2019 May 6;216(5):1154-1169. doi: 10.1084/jem.20190185. Epub 2019 Apr 8.

    PMID: 30962246RESULT

  • Kaplowitz ET, Ferguson S, Guerra M, Laskin CA, Buyon JP, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Merrill JT, Katz P, Salmon JE. Contribution of Socioeconomic Status to Racial/Ethnic Disparities in Adverse Pregnancy Outcomes Among Women With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2018 Feb;70(2):230-235. doi: 10.1002/acr.23263. Epub 2017 Dec 29.

    PMID: 28480528RESULT

  • Davis-Porada J, Kim MY, Guerra MM, Laskin CA, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Sawitzke A, Merrill JT, Buyon JP, Salmon JE. Low frequency of flares during pregnancy and post-partum in stable lupus patients. Arthritis Res Ther. 2020 Mar 19;22(1):52. doi: 10.1186/s13075-020-2139-9.

    PMID: 32188491DERIVED

  • Yelnik CM, Lambert M, Drumez E, Le Guern V, Bacri JL, Guerra MM, Laskin CA, Branch DW, Sammaritano LR, Morel N, Guettrot-Imbert G, Launay D, Hachulla E, Hatron PY, Salmon JE, Costedoat-Chalumeau N. Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome. Lupus. 2018 Sep;27(10):1679-1686. doi: 10.1177/0961203318787032. Epub 2018 Jul 17.

    PMID: 30016929DERIVED

  • Andrade D, Kim M, Blanco LP, Karumanchi SA, Koo GC, Redecha P, Kirou K, Alvarez AM, Mulla MJ, Crow MK, Abrahams VM, Kaplan MJ, Salmon JE. Interferon-alpha and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia. Arthritis Rheumatol. 2015 Apr;67(4):977-87. doi: 10.1002/art.39029.

    PMID: 25603823DERIVED

  • Michael D Lockshin, Cohn E, Aslam A, Buyon JP, Salmon JE. Sex ratios among children of lupus pregnancies. Arthritis Rheum. 2013 Jan;65(1):282. doi: 10.1002/art.37718. No abstract available.

    PMID: 23044629DERIVED

  • Salmon JE, Heuser C, Triebwasser M, Liszewski MK, Kavanagh D, Roumenina L, Branch DW, Goodship T, Fremeaux-Bacchi V, Atkinson JP. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. PLoS Med. 2011 Mar;8(3):e1001013. doi: 10.1371/journal.pmed.1001013. Epub 2011 Mar 22.

    PMID: 21445332DERIVED

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, whole blood, RNA, urine

MeSH Terms

Conditions

Lupus Erythematosus, SystemicAntiphospholipid Syndrome

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Jane E. Salmon, M.D.

    Hospital for Special Surgery, New York

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta M. Guerra, MS

CONTACT

212-774-7361guerram@hss.edu

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 20, 2005

Study Start

September 1, 2003

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Last Updated

April 28, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

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.

Locations

CA(1)US(8)GB(1)