Condition category
Haematological Disorders
Date applied
25/01/2019
Date assigned
02/08/2019
Last edited
02/08/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Sickle Cell Disease (SCD) is a serious inherited blood disorder affecting red blood cells. When oxygen levels drop the red cells become abnormally shaped and unable to move through the blood vessels easily. Blood and oxygen do not reach body organs, resulting in episodes of severe pain and other complications. Pregnant women with SCD have an increased risk of both sickle and pregnancy complications, including raised blood pressure. Their babies may grow more slowly in the womb, are more likely to be born early and need special care, and have a higher risk of dying. The only treatments currently available for women with SCD are Hydroxycarbamide (which cannot be used during pregnancy) and blood transfusion. Currently, blood transfusion is only used during pregnancy to treat emergency complications. Giving blood transfusions throughout pregnancy could improve outcomes for both mother and babies. In Serial Prophylactic Exchange Blood Transfusion (SPEBT), sickle blood is mechanically removed and simultaneously replaced with donor red cells. The researchers wish to conduct a trial of SPEBT given every 6-10 weeks, starting before 18 weeks of pregnancy, compared to standard care, and measure outcomes for the women (e.g. hospital admission, frequency of crisis) and their infants (e.g. early delivery, birthweight). Before they embark on a large multi-centre study the aim of this study is to find out whether this is feasible.

Who can participate?
Pregnant women aged 18 and over with SCD

What does the study involve?
Participants are randomly allocated to have either SPEBT or standard care. The researchers assess how many pregnant women are willing to join the study and how many participants remain part of the study until the end to give an indication of how many participants they may be able to recruit in the future trial.

What are the possible benefits and risks of participating?
Blood transfusions are regularly used in the clinical care of women with SCD during pregnancy. In the UK, many precautions are taken to make sure any blood transfusion is as safe as possible. The main risk from a transfusion is that the wrong blood is given by accident. To avoid this happening the clinical staff will make careful identification checks. The risk of contracting a disease, such as hepatitis or human immunodeficiency virus (HIV), is extremely low. There may be minor reactions of blood transfusion such as skin rash or a minor fever. These can be treated easily with paracetamol and antihistamines. Occasionally a patient experiences a delayed transfusion reaction which may occur within the first two weeks of being transfused. Patients will be informed of the possible symptoms of a delayed transfusion reaction and asked to attend hospital immediately for assessment should these symptoms occur. Possible complications specific to exchange blood transfusions are light-headedness, fainting and a tingling sensation on lips and fingers. This is due to the anticoagulant used, which lowers calcium levels in the blood. Calcium tablets or an injection may be given during the procedure to prevent this.

Where is the study run from?
Guy's and St Thomas' NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
April 2019 to April 2021

Who is funding the study?
NIHR Research for Patient Benefit Programme (UK)

Who is the main contact?
Dr Eugene Oteng-Ntim
eugene.oteng-ntim@gstt.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Eugene Oteng-Ntim

ORCID ID

Contact details

Guy's and St Thomas' NHS Foundation Trust
Westminster Bridge Road
London
SE1 7EH
United Kingdom
+44 (0)20 7188 6874
eugene.oteng-ntim@gstt.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

NCT03975894

Protocol/serial number

CPMS: 39564; V1.0 24/10/2018

Study information

Scientific title

A feasibility trial of serial prophylactic exchange blood transfusion (SPEBT) in pregnant women with sickle cell disease (SCD) aiming to improve maternal and infant outcomes

Acronym

TAPS2

Study hypothesis

Is it feasible to conduct an RCT to establish the effectiveness and cost-effectiveness of Serial Prophylactic Exchange Blood Transfusion (SPEBT) from the first trimester (under or equal to 18 weeks of gestation) improving clinical and cost effectiveness outcomes in pregnant women with sickle cell disease and their newborn babies?

Ethics approval

Approved 28/03/2019, London – Surrey Borders Research Ethics Committee (Research Ethics Committee (REC) London Centre, Ground Floor, Skipton House, 80 London Road, London SE1 6LH, UK; Tel: +44 (0)207 972 2568; Email: NRESCommittee.London-SurreyBorders@nhs.net), REC ref: 18/LO/2070

Study design

Individually randomised two-arm feasibility trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Sickle Cell Disease in pregnancy

Intervention

Women allocated to the intervention will receive serial prophylactic exchange blood transfusion starting from or before 18 weeks of gestation. These serial exchange blood transfusions will be performed using automated erythrocytopheresis, approximately every 6-10 weeks, aiming to maintain HbS% below 30%. The number of units will depend on patient size and pre-transfusion HbS%. The transfusion will be carried out on the haematology day unit prior to 20 weeks and on the antenatal day unit after 20 weeks gestation and will be performed by trained apheresis staff using standard operating procedures. Venous access will be via peripheral access if possible or by femoral line access if not.

Women in the control group will receive standard care for sickle cell disease in pregnancy according to NICE guidelines.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Feasibility outcome:
1. Recruitment rate, measured as women eligible: women randomised, measured at baseline

Secondary outcome measures

Feasibility outcomes:
1. Reasons for refusal assessed by self-report at baseline
2. Rate of attrition measured as the number of participants consented who remain in the study until 6 weeks postpartum, measured at 6 weeks postpartum
3. Reasons for attrition assessed by self-report at study drop-out
4. Protocol adherence measured as the number of participants in the intervention arm who receive the intervention as outlined in the protocol, measured at pregnancy end/birth

Clinical outcomes for the woman:
1. Maternal hospital admissions: antenatal and postnatal inpatient stays measured every 6-8 weeks from enrolment to 6 weeks postpartum
2. Frequency and severity of painful crisis: self-reported pain (mild/moderate/severe/extremely severe) and use of opioid analgesics, measured every 6-8 weeks from enrolment to 6 weeks postpartum
3. Mode of birth: delivery type extracted from hospital records (assessed at birth)
4. SCD-related complications: report of any SCD-related complications (acute chest syndrome, stroke, pre-eclampsia, venous thromboembolism) as notified by health professionals or extracted from hospital records (assessed at birth)

Clinical outcomes for the infant:
1. Fetal demise/stillbirth, as notified by health professional or extracted from hospital records, assessed at pregnancy end
2. Infant birthweight: birthweight extracted from hospital records, assessed at birth
3. Gestation at birth: gestation in weeks and days extracted from hospital records, assessed at birth
4. NICU/critical care admission: extracted from hospital records or self-reported by mother at 6 weeks postpartum

Safety outcomes:
1. Transfusion reaction: reported by health professional (incident reporting).
2. Delayed haemolytic transfusion reaction: reported by health professional (incident reporting).
3. Alloimmunisation: irregular presence of red cell antibodies as measured by routine blood test measured every 6-8 weeks from enrolment to 6 weeks postpartum

Overall trial start date

01/04/2019

Overall trial end date

30/04/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Pregnant women with SCD (all genotypes) with confirmatory laboratory results
2. Singleton pregnancies
3. 18 years or older
4. Gestation 18 weeks or below
5. Able to give informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

50

Participant exclusion criteria

1. Women on long term transfusion programme prior to pregnancy for amelioration of SCD
2. Women unable to receive blood transfusion for social, religious or clinical reasons
3. Pregnant women with sickle cell disease with current diagnosis of major medical or psychiatric comorbidity which in the randomising clinician's opinion renders them unable to enter trial

Recruitment start date

02/05/2019

Recruitment end date

01/10/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
Westminster Bridge Road
London
SE1 7EH
United Kingdom

Sponsor information

Organisation

Guy's and St Thomas' NHS Foundation Trust

Sponsor details

Westminster Bridge Road
London
SE 1 7EH
United Kingdom
+44 (0)20 7188 6874
eugene.oteng-ntim@gstt.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Research for Patient Benefit Programme

Alternative name(s)

NIHR Research for Patient Benefit Programme, RfPB

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Members of the Core Project Team, PPI Group and collaborators will advise and guide the development of a dissemination strategy through the partnerships developed during the planning of this application. The researchers will submit a manuscript, complying with CONSORT guidance, to high impact peer-reviewed clinical and methodological journals. Abstracts will be submitted to major conferences including the RCOG annual conference, British Maternal and Fetal Medicine conference, American Society of Haematology conference, and United Kingdom Haemoglobinopathy and obstetric haematology conferences. The study protocol and reports will be circulated to all haematology consultants, NHS clinicians, service managers and commissioners through the RCOG and NHS Clinical Commissioning Groups. The researchers will invite key stakeholders, including local service users, to a dissemination event to discuss findings and implications for the management of SCD in pregnancy. Links to all findings will be made available on KCL, KHP, LSHTM, and SCS websites. With input from our PPI Group, SCS and local MSLC, they will produce a lay research summary. This will be disseminated to user groups such as the UK Haemoglobinopathy Forum and Sickle Cell Society, and the Dora Foundation (patient-founded charity for SCD, MK is the lead), and to research participants and patient groups at collaborating hospitals. The researchers' contacts with local maternity network groups and community sickle cell teams in London will also be utilised to ensure we reach all local sickle cell service users. Outcomes and criteria to progress to definitive trial will be discussed with RDS South Central, London South CLRN, the RCOG and RCOG Maternal Medicine Clinical study group and specialist commissioners and centres and networks likely to recruit to the definitive trial. If there is an agreement to support progression to a definitive trial, the researchers will contact interested groups and sites for a multicentre trial, and an application for funding will be submitted.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/08/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/08/2019: Trial's existence confirmed by the NIHR.