SCRIPT: Sickle Cell Risk in Pregnancy Tool (SCRIPT)

November 25, 2024 updated by: Mount Sinai Hospital, Canada

Prediction of Adverse Outcomes in Pregnancies of Individuals With Sickle Cell Disease - SCRIPT: Sickle Cell Risk in Pregnancy Tool

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

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

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Providence Health Care
    • Quebec
      • Montréal, Quebec, Canada, H2X 0C1
        • Centre Hospitalier de l'Université de Montréal
  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Johns Hopkins University

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

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Pregnant Individuals with Sickle Cell Disease (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+-thalassemia)

Description

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)

Exclusion Criteria:

  • Inability to confirm SCD genotype
  • Incomplete medical records.

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pregnancies of Individuals with Sickle Cell Disease
Other: Non-Interventional
Non-Interventional

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of Adverse Pregnancy Outcome
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of the following events first noted during the pregnancy within the study period: acute anemia (yes, no), cardiac complication (yes, no), pulmonary complication (yes, no), hepatobiliary complication (yes, no), MSK complication (yes, no), splenic complication (yes, no), neurologic complication (yes, no), renal complication (yes, no); multi-organ failure (yes, no), venous thromboembolism (yes, no), vaso-occlusive event with admission (yes, no), red cell transfusion (yes, no), maternal mortality (yes, no), hypertensive disorder of pregnancy (yes, no), preterm birth (yes, no), small for gestational age (yes, no), or perinatal mortality (yes, no); defined based on published classifications.
During pregnancy (until delivery of infant, up to 42 weeks of gestation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of Acute Anemia
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: hyperhemolysis [clinical diagnosis], acute splenic sequestration; hepatic sequestration, or aplastic crisis; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Cardiac Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: congestive heart failure, cardiomyopathy, cardiomegaly, or arrhythmia; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Pulmonary Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: acute chest syndrome; pneumonia, or pulmonary hypertension; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Hepato-Biliary Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: cholecystitis, cholelithiasis; cholecystectomy; cholestasis of pregnancy, or viral hepatitis; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Musculo-Skeletal Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: avascular necrosis, ulcer, myositis, or osteomyelitis; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Neurologic Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: silent cerebral infarct, cerebrovascular accident, cerebral aneurysm, transient ischemic attack, or Moya-Moya syndrome; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Renal Complications
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: acute kidney injury, proteinuria, pyelonephritis, or hematuria; defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Multi-Organ Failure
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Consultant's opinion in chart note specifying a diagnosis of "MOF" during current study pregnancy; clinical diagnosis
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Venous Thromboembolism
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: deep vein thrombosis, pulmonary embolism, atypical site venous thrombosis, or cerebral venous sinus thrombosis (CVST); defined based on published classification
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Vaso-Occlusive Event with Admission
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Vaso-Occlusive Event (VOE): New onset pain lasting >4 hrs in current study pregnancy, for which there is no explanation other than vaso-occlusion, and which requires presentation for acute care - patient self-report
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Provision of Red Blood Cell Transfusion
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: simple transfusion in pregnancy, exchange transfusion (manual exchange or erythrocytapheresis), or prophylactic transfusion
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Occurrence of Maternal Mortality
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation) and continuing to 6 months postpartum
Maternal death during current study pregnancy and up to 6 months postpartum
During pregnancy (until delivery of infant, up to 42 weeks of gestation) and continuing to 6 months postpartum
Presence of Hypertensive Disorder of Pregnancy
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Yes, if any of: Gestational Hypertension (gHTN) [persistent de novo HTN over 20 weeks' GA in absence of features of preeclampsia], Pre-eclampsia (PET) [gHTN + >1 new onset conditions >20 weeks GA - proteinuria or maternal organ/uteroplacental dysfunction], Eclampsia [new onset seizures in context of pre-eclampsia]; or HELLP Syndrome [Evidence of Hemolysis, Elevated Liver Enzymes, Low Platelets in context of pre-eclampsia]
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Occurrence of Preterm Birth
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Preterm birth (< 37+0 weeks GA) during current study pregnancy
During pregnancy (until delivery of infant, up to 42 weeks of gestation)
Presence of Small for Gestational Age (SGA) Size
Time Frame: At delivery of infant
Birthweight <10th centile for gestational age
At delivery of infant
Occurrence of Perinatal Mortality
Time Frame: During pregnancy (until delivery of infant, up to 42 weeks of gestation) and up to 28 days after birth)
Intrauterine fetal demise (IUFD) [absence of FHR at or after 20 weeks' gestation] or Neonatal Death (NND) [death before 28 days of life, following live birth]
During pregnancy (until delivery of infant, up to 42 weeks of gestation) and up to 28 days after birth)

Collaborators and Investigators

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

Sponsor

Mount Sinai Hospital, Canada

Collaborators

Johns Hopkins University
Centre hospitalier de l'Université de Montréal (CHUM)
St. Paul's Hospital, Vancouver (Providence Health Care)

Investigators

  • Principal Investigator: A. Kinga Malinowski, MD, MSc, Mount Sinai Hospital

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

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 (Actual)

September 1, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 26, 2024

First Submitted That Met QC Criteria

July 25, 2024

First Posted (Actual)

July 31, 2024

Study Record Updates

Last Update Posted (Estimated)

November 27, 2024

Last Update Submitted That Met QC Criteria

November 25, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCRIPT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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