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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT00198068
Other study ID # 2014-309
Secondary ID R01AR049772
Status Recruiting
Phase
First received
Last updated
Start date September 2003
Est. completion date March 2025

Study information

Verified date April 2024
Source Hospital for Special Surgery, New York
Contact Marta M. Guerra, MS
Phone 212-774-7361
Email guerram@hss.edu
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 700
Est. completion date March 2025
Est. primary completion date March 2025
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 45 Years
Eligibility Inclusion Criteria: - Patient pregnant with live intrauterine pregnancy, as defined by positive test for elevated ß-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-ß2GPI: 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 Design


Locations

Country Name City State
Canada Mt. Sinai Hospital Toronto Ontario
United Kingdom Guy's & St Thomas' NHS Foundation Trust London
United States Johns Hopkins Hospital Baltimore Maryland
United States Northwestern University Chicago Illinois
United States University of Chicago Chicago Illinois
United States Columbia University Medical Center New York New York
United States Hospital for Special Surgery New York New York
United States NYU Langone Medical Center/Hospital for Joint Diseases New York New York
United States Oklahoma Medical Research Foundation Oklahoma City Oklahoma
United States University of Utah Salt Lake City Salt Lake City Utah

Sponsors (2)

Lead Sponsor Collaborator
Hospital for Special Surgery, New York National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (12)

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 — View Citation

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 C — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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, Blanken — View Citation

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 Syste — View Citation

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 pa — View Citation

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 erythema — View Citation

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 patie — View Citation

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 — View Citation

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. — View Citation

* Note: There are 12 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary Neonatal death Neonatal death prior to hospital discharge and due to complications of prematurity Time of neonatal death
Primary 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
Primary 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 Gestational age Gestational age (weeks and days) at the end of pregnancy End of pregnancy
Secondary Birth weight Birth weight End of pregnancy
Secondary Number of days neonate requires positive pressure ventilation Number of days neonate requires positive pressure ventilation Neonate discharge from hospital
Secondary Total number of days neonate is hospitalized Total number of days neonate is hospitalized Neonate discharge from hospital
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