Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ENROLLING_BY_INVITATION
Total Enrollment
1000 participants
Study Classification
OBSERVATIONAL
Study Start Date
2024-09-01
Study Completion Date
2026-12-31
Brief Summary
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Sickle Cell Disease (SCD), common in persons of Black ancestry, affects the shape of hemoglobin, the oxygen-carrying part of red blood cells (RBC). It is characterized by many complications, the most dreaded of which are related to pregnancy - affecting both the mother and unborn child. Compared to those without SCD, people with SCD have more adverse pregnancy outcomes (APO): 6x maternal mortality, 2x preeclampsia \& preterm birth, 4x risk of having a baby not growing well in the womb \& stillbirth. There is also greater need for access to care (7x higher hospitalization often multiple times lasting days to months). Yet up to 30% of SCD pregnancies are uncomplicated.
Treatments in pregnancy are limited and carry risks. A method to distinguish pregnancies at high-risk of APO that may benefit from these potentially risky treatments, from those likely to be uncomplicated, is urgently needed. To meet this need, the investigators developed a calculator to estimate pregnancy complication risk, using single-centre data. Its accuracy and precision will now be evaluated with international information from several centers by testing the calculator, and adjusting it as needed, using already available pregnancy-data from study centres in several countries. Those age \>16 years, who have a confirmed SCD genotype, pregnancy with one baby, and pregnancy care and birth at a participating study centre will be included. Pregnancy care for the participants will be up to their doctors, with no changes based on the study. SCRIPT - the new tool - will guide future care by predicting who may benefit from specific treatments, reducing harm to low-risk individuals \& will allow selection of high-risk patients for a future trials to determine whether currently available and novel treatments in well-selected patients can improve APO sufficiently to balance treatment-related harms.
Treatments in pregnancy are limited and carry risks. A method to distinguish pregnancies at high-risk of APO that may benefit from these potentially risky treatments, from those likely to be uncomplicated, is urgently needed. To meet this need, the investigators developed a calculator to estimate pregnancy complication risk, using single-centre data. Its accuracy and precision will now be evaluated with international information from several centers by testing the calculator, and adjusting it as needed, using already available pregnancy-data from study centres in several countries. Those age \>16 years, who have a confirmed SCD genotype, pregnancy with one baby, and pregnancy care and birth at a participating study centre will be included. Pregnancy care for the participants will be up to their doctors, with no changes based on the study. SCRIPT - the new tool - will guide future care by predicting who may benefit from specific treatments, reducing harm to low-risk individuals \& will allow selection of high-risk patients for a future trials to determine whether currently available and novel treatments in well-selected patients can improve APO sufficiently to balance treatment-related harms.
Detailed Description
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Sickle Cell Disease (SCD) is the most common haemoglobinopathy; predominantly affecting persons of African descent(1). In comparison to those without SCD, pregnant persons with SCD have a six-fold higher risk of mortality, twice the risk of preeclampsia and preterm birth, and nearly a four-fold risk of having a small for gestational age infant or experiencing stillbirth(2,3). Furthermore, there is a higher rate of resource utilization in this group, with nearly 50% of pregnancies complicated by at least one antenatal admission and an overall seven-fold higher hospitalization risk compared to pregnancies without SCD(4,5). These admissions are most commonly secondary to vaso-occlusive events or anemia, can occur on multiple occasions, and can last days to months(4,5).
During pregnancy, red blood cell (RBC) transfusion remains the only recommended intervention(6), with some evidence suggesting that prophylactic transfusion may modify adverse pregnancy outcomes (APOs)(7,8), with a possible positive effect on hospitalization rates through decreased complications, though this requires further study. However, transfusion is not without risk. Beyond its typically-feared infectious complications(9), transfusion in SCD is associated with alloimmunization rates of over 30%(10-12), can induce life-threatening hyperhemolysis(13), and will eventually lead to iron overload(14). At the same time, up to 30% of pregnancies in individuals with SCD remain uncomplicated(2,3,15,16).
A tool is thus urgently needed to separate high-risk individuals who would benefit from transfusion from low-risk individuals who would accrue transfusion risks with minimal, if any benefit. Using a single-centre cohort, the investigators developed maternal and fetal risk prediction models, as the first step in permitting the selection of patients most likely to benefit from transfusion(16). Ultimately, a multi-center international randomized controlled trial (RCT) is required to determine the benefits of prophylactic transfusion in this setting; yet, before such an RCT is conceived, the model(s) must be refined and validated with a larger sample to allow for appropriate participant selection.
The investigators proposed a multicenter international cohort study to enhance the predictive capacity and validate the current model(s) within the participating centers. The academic centers (located in Canada, USA, and France), have multi-disciplinary experts dedicated to managing pregnant persons with SCD, and the combination of MFM and Haematology site co-leads provides essential interdisciplinary expertise with synergistic medical and obstetric perspectives.
Once completed, the Sickle Cell Risk In Pregnancy Tool (SCRIPT) will inform medical decisions regarding transfusion and will set the stage for appropriate selection of high-risk individuals for inclusion in an RCT aimed to definitively determine whether prophylactic transfusion in well-selected pregnant individuals with SCD does indeed improve APOs to the degree that would balance its potential associated harms.
During pregnancy, red blood cell (RBC) transfusion remains the only recommended intervention(6), with some evidence suggesting that prophylactic transfusion may modify adverse pregnancy outcomes (APOs)(7,8), with a possible positive effect on hospitalization rates through decreased complications, though this requires further study. However, transfusion is not without risk. Beyond its typically-feared infectious complications(9), transfusion in SCD is associated with alloimmunization rates of over 30%(10-12), can induce life-threatening hyperhemolysis(13), and will eventually lead to iron overload(14). At the same time, up to 30% of pregnancies in individuals with SCD remain uncomplicated(2,3,15,16).
A tool is thus urgently needed to separate high-risk individuals who would benefit from transfusion from low-risk individuals who would accrue transfusion risks with minimal, if any benefit. Using a single-centre cohort, the investigators developed maternal and fetal risk prediction models, as the first step in permitting the selection of patients most likely to benefit from transfusion(16). Ultimately, a multi-center international randomized controlled trial (RCT) is required to determine the benefits of prophylactic transfusion in this setting; yet, before such an RCT is conceived, the model(s) must be refined and validated with a larger sample to allow for appropriate participant selection.
The investigators proposed a multicenter international cohort study to enhance the predictive capacity and validate the current model(s) within the participating centers. The academic centers (located in Canada, USA, and France), have multi-disciplinary experts dedicated to managing pregnant persons with SCD, and the combination of MFM and Haematology site co-leads provides essential interdisciplinary expertise with synergistic medical and obstetric perspectives.
Once completed, the Sickle Cell Risk In Pregnancy Tool (SCRIPT) will inform medical decisions regarding transfusion and will set the stage for appropriate selection of high-risk individuals for inclusion in an RCT aimed to definitively determine whether prophylactic transfusion in well-selected pregnant individuals with SCD does indeed improve APOs to the degree that would balance its potential associated harms.
Conditions
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Sickle Cell Disease
Pregnancy, High Risk
Pregnancy Complications
Study Design
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Observational Model Type
COHORT
Study Time Perspective
RETROSPECTIVE
Study Groups
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Pregnancies of Individuals with Sickle Cell Disease
Non-Interventional
Intervention Type
OTHER
Non-Interventional
Interventions
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Non-Interventional
Non-Interventional
Intervention Type
OTHER
Eligibility Criteria
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Inclusion Criteria
* Age \>16 years
* HbSS, HbSC, HbS/β0-thalassemia, HbS/β+-thalassemia confirmed on Hb electrophoresis, high performance liquid chromatography, capillary electrophoresis, or genetic testing
* Records of pregnancy care and birth at a participating centre
* Pregnancy continuing to at least 16+0 weeks' gestation (41,42)
* HbSS, HbSC, HbS/β0-thalassemia, HbS/β+-thalassemia confirmed on Hb electrophoresis, high performance liquid chromatography, capillary electrophoresis, or genetic testing
* Records of pregnancy care and birth at a participating centre
* Pregnancy continuing to at least 16+0 weeks' gestation (41,42)
Exclusion Criteria
* Inability to confirm SCD genotype
* Incomplete medical records.
* Incomplete medical records.
Minimum Eligible Age
16 Years
Maximum Eligible Age
60 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
No
Sponsors
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Johns Hopkins University
OTHER
Sponsor Role
collaborator
Centre hospitalier de l'Université de Montréal (CHUM)
OTHER
Sponsor Role
collaborator
St. Paul's Hospital, Vancouver (Providence Health Care)
UNKNOWN
Sponsor Role
collaborator
Mount Sinai Hospital, Canada
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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A. Kinga Malinowski, MD, MSc
Role: PRINCIPAL_INVESTIGATOR
MOUNT SINAI HOSPITAL
Locations
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Johns Hopkins University
Baltimore, Maryland, United States
Site Status
Providence Health Care
Vancouver, British Columbia, Canada
Site Status
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, Canada
Site Status
Countries
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United States
Canada
References
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Boafor TK, Olayemi E, Galadanci N, Hayfron-Benjamin C, Dei-Adomakoh Y, Segbefia C, Kassim AA, Aliyu MH, Galadanci H, Tuuli MG, Rodeghier M, DeBaun MR, Oppong SA. Pregnancy outcomes in women with sickle-cell disease in low and high income countries: a systematic review and meta-analysis. BJOG. 2016 Apr;123(5):691-8. doi: 10.1111/1471-0528.13786. Epub 2015 Dec 15.
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BACKGROUND
Oteng-Ntim E, Meeks D, Seed PT, Webster L, Howard J, Doyle P, Chappell LC. Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis. Blood. 2015 May 21;125(21):3316-25. doi: 10.1182/blood-2014-11-607317. Epub 2015 Mar 23.
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BACKGROUND
Sun PM, Wilburn W, Raynor BD, Jamieson D. Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol. 2001 May;184(6):1127-30. doi: 10.1067/mob.2001.115477.
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BACKGROUND
Yu CK, Stasiowska E, Stephens A, Awogbade M, Davies A. Outcome of pregnancy in sickle cell disease patients attending a combined obstetric and haematology clinic. J Obstet Gynaecol. 2009 Aug;29(6):512-6. doi: 10.1080/01443610903003175.
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BACKGROUND
Chou ST, Alsawas M, Fasano RM, Field JJ, Hendrickson JE, Howard J, Kameka M, Kwiatkowski JL, Pirenne F, Shi PA, Stowell SR, Thein SL, Westhoff CM, Wong TE, Akl EA. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020 Jan 28;4(2):327-355. doi: 10.1182/bloodadvances.2019001143.
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Malinowski AK, Shehata N, D'Souza R, Kuo KH, Ward R, Shah PS, Murphy K. Prophylactic transfusion for pregnant women with sickle cell disease: a systematic review and meta-analysis. Blood. 2015 Nov 19;126(21):2424-35; quiz 2437. doi: 10.1182/blood-2015-06-649319. Epub 2015 Aug 24.
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BACKGROUND
Vianello A, Vencato E, Cantini M, Zanconato G, Manfrin E, Zamo A, Zorzi F, Mazzi F, Martinelli N, Cavaliere E, Monari F, Venturelli D, Ferrara F, Olivieri O, De Franceschi L. Improvement of maternal and fetal outcomes in women with sickle cell disease treated with early prophylactic erythrocytapheresis. Transfusion. 2018 Sep;58(9):2192-2201. doi: 10.1111/trf.14767. Epub 2018 Jul 8.
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BACKGROUND
Chou ST. Transfusion therapy for sickle cell disease: a balancing act. Hematology Am Soc Hematol Educ Program. 2013;2013:439-46. doi: 10.1182/asheducation-2013.1.439.
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BACKGROUND
Kacker S, Ness PM, Savage WJ, Frick KD, Shirey RS, King KE, Tobian AA. Economic evaluation of a hypothetical screening assay for alloimmunization risk among transfused patients with sickle cell disease. Transfusion. 2014 Aug;54(8):2034-44. doi: 10.1111/trf.12585. Epub 2014 Feb 27.
Reference Type
BACKGROUND
Yazdanbakhsh K, Ware RE, Noizat-Pirenne F. Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management. Blood. 2012 Jul 19;120(3):528-37. doi: 10.1182/blood-2011-11-327361. Epub 2012 May 4.
Reference Type
BACKGROUND
Balbuena-Merle R, Hendrickson JE. Red blood cell alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease. Transfus Clin Biol. 2019 May;26(2):112-115. doi: 10.1016/j.tracli.2019.02.003. Epub 2019 Feb 22.
Reference Type
BACKGROUND
Danaee A, Inusa B, Howard J, Robinson S. Hyperhemolysis in Patients With Hemoglobinopathies: A Single-Center Experience and Review of the Literature. Transfus Med Rev. 2015 Oct;29(4):220-30. doi: 10.1016/j.tmrv.2015.06.001. Epub 2015 Jun 19.
Reference Type
BACKGROUND
Tavares AHJ, Benites BD, Fertrin KY. Myocardial Iron Overload in Sickle Cell Disease: A Rare But Potentially Fatal Complication of Transfusion. Transfus Med Rev. 2019 Jul;33(3):170-175. doi: 10.1016/j.tmrv.2019.04.001. Epub 2019 May 2.
Reference Type
BACKGROUND
Silva FAC, Ferreira ALCG, Hazin-Costa MF, Dias MLG, Araujo AS, Souza AI. Adverse clinical and obstetric outcomes among pregnant women with different sickle cell disease genotypes. Int J Gynaecol Obstet. 2018 Oct;143(1):89-93. doi: 10.1002/ijgo.12626. Epub 2018 Aug 6.
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BACKGROUND
Malinowski AK, Kuo KHM, Tomlinson GA, Palcu P, Ward R, Shehata N. Distinct maternal and fetal pregnancy outcomes in women with sickle cell disease can be predicted using routine clinical and laboratory data. Br J Haematol. 2021 Sep;194(6):1063-1073. doi: 10.1111/bjh.17607. Epub 2021 Jun 14.
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BACKGROUND
Odendaal H, Wright C, Brink L, Schubert P, Geldenhuys E, Groenewald C. Association of late second trimester miscarriages with placental histology and autopsy findings. Eur J Obstet Gynecol Reprod Biol. 2019 Dec;243:32-35. doi: 10.1016/j.ejogrb.2019.10.024. Epub 2019 Oct 22.
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Roberge S, Nicolaides KH, Demers S, Villa P, Bujold E. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol. 2013 May;41(5):491-9. doi: 10.1002/uog.12421.
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Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, Johnson CS, Rogers ZR, Smith-Whitley K, Wang WC, Telen MJ; Investigators, Comprehensive Sickle Cell Centers. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol. 2010 Jan;85(1):6-13. doi: 10.1002/ajh.21550.
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Magee LA, Pels A, Helewa M, Rey E, von Dadelszen P; Canadian Hypertensive Disorders of Pregnancy Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary. J Obstet Gynaecol Can. 2014 May;36(5):416-41. doi: 10.1016/s1701-2163(15)30588-0. English, French.
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Kramer MS, Platt RW, Wen SW, Joseph KS, Allen A, Abrahamowicz M, Blondel B, Breart G; Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001 Aug;108(2):E35. doi: 10.1542/peds.108.2.e35.
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Other Identifiers
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SCRIPT
Identifier Type: -
Identifier Source: org_study_id