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Aspirin and Neutrophils in Preeclampsia

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ClinicalTrials.gov Identifier: NCT04974892
Recruitment Status : Not yet recruiting
First Posted : July 23, 2021
Last Update Posted : August 4, 2021
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

Tracking Information
First Submitted Date May 21, 2021
First Posted Date July 23, 2021
Last Update Posted Date August 4, 2021
Estimated Study Start Date September 1, 2021
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 28, 2021)
  • To longitudinally define the neutrophil profile in high-risk patients given low dose aspirin (LDA) at ≤16 weeks. [ Time Frame: 2 years ]
    To address the first objective, to assess the neutrophil profile in high-risk patients given LDA at ≤16 weeks, a longitudinal analyses will be undertaken of neutrophils taken from participants at high-risk of PE (as identified at their pregnancy booking appointment). The first blood test will occur prior to aspirin commencement and be repeated at 3 other time points in pregnancy. These longitudinal analyses will identify cumulative changes in neutrophils following the commencement of aspirin treatment and pinpoint key timepoints of aspirin on neutrophil biology.
  • To define the neutrophil profile in a cohort of high-risk patients who have not responded to low dose aspirin (LDA) and have gone on to develop PE. [ Time Frame: 2 years ]
    To address the second objective (to assess the neutrophil profile in a cohort of high-risk patients who have not responded to LDA and have gone on to develop PE), 20 LDA non-responders subsequently develop PE will be identified.
Original Primary Outcome Measures
 (submitted: July 16, 2021)
  • To longitudinally define the neutrophil profile in high-risk women given low dose aspirin (LDA) at ≤16 weeks. [ Time Frame: 2 years ]
    To address the first objective, to assess the neutrophil profile in high-risk women given LDA at ≤16 weeks, we will conduct a longitudinal analysis of neutrophils taken from women at high-risk of PE (as identified at their pregnancy booking appointment). The first blood test will occur prior to aspirin commencement and be repeated at 3 other time points in pregnancy. These longitudinal analyses will identify cumulative changes in neutrophils following the commencement of aspirin treatment and pinpoint key timepoints of aspirin on neutrophil biology. Based on our data in Figure 2, n=40 will provide us a power >0.95 of identifying an altered neutrophil phenotype associated with PE.
  • To define the neutrophil profile in a cohort of high-risk women who have not responded to low dose aspirin (LDA) and have gone on to develop PE. [ Time Frame: 2 years ]
    To address the second objective (to assess the neutrophil profile in a cohort of high-risk women who have not responded to LDA and have gone on to develop PE), we will identify 20 LDA non-responders subsequently develop PE.
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Aspirin and Neutrophils in Preeclampsia
Official Title Investigating the Role of Neutrophils in Aspirin Treatment for Women at High Risk of Preeclampsia
Brief Summary

The exact mechanisms by which aspirin prevents the development of preeclampsia in high-risk patients are currently not fully known. Furthermore, a small proportion of high-risk patients who are on low-dose aspirin (LDA) still go on to develop preeclampsia (PE).

This longitudinal observational study will assess the immune profile in participants who are taking low dose aspirin (LDA) in pregnancy. As part of routine care, patients at high risk of developing preeclampsia are treated with LDA from 16 weeks gestation.

The study will be conducted at Barts Health National Health Service (NHS) Trust. The study population will comprise of 2 groups of participants:

  1. Those who respond to LDA and do not develop preeclampsia (responders)
  2. Participants who do not respond to LDA and develop preeclampsia (non responders)

Participants will be consented at their booking appointment. Participants will be eligible if they have a singleton pregnancy and are aged over 18 years. They will have an additional blood sample taken at 12, 20, 28 and 36 weeks gestation.

The blood samples will be tested to assess immune cell function, metabolism and genetics. This will identify cumulative changes in immunobiology at key time points in pregnancy.

Detailed Description

The exact mechanisms by which aspirin prevents the development of PE in high-risk patients are currently not fully known. Furthermore, a small proportion of high-risk patients who are on low-dose aspirin still go on to develop PE. This is a big unmet need because although it is known that this treatment is working for some patients, it is not known how it's working in these patients and also why a proportion of patients don't respond to this treatment. If the key mechanisms by which aspirin treatment is beneficial in patients at high risk of PE can be identifies, this will lead to better information for clinicians of why this treatment works and this could then be conveyed to the patient. Moreover, if key differences can be identified between aspirin responders and non-responders, novel therapeutic targets could be developed that could work for all patients at high risk of PE.

One of the main anti-inflammatory actions of aspirin is the release of aspirin-triggered lipoxin (ATL). The receptor for ATL (FPR2/ALX) is highly expressed on neutrophils, suggesting that the anti-inflammatory action of this drug is mediated via neutrophils. The investigators have previously shown that neutrophils are important in mediating anti-inflammatory responses in PE. Thus, taken together, the hypothesis is that neutrophils are key to understanding the mechanisms involved in the use of low-dose aspirin (LDA) treatment in patients at high risk of developing PE and key to understanding why this treatment does not work in some high-risk patients. This hypothesis will be addressed by two objectives both of which will entail in-depth profiling of neutrophils.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 24 Weeks
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients at high risk of developing preeclampsia in pregnancy who are started on low dose aspirin at ≤16 weeks.
Condition
  • Preeclampsia
  • Neutrophil
  • Immunology
  • Pregnancy
Intervention Diagnostic Test: Blood test
Blood tests will be taken at 12, 20, 28 and 36 weeks gestation to assess the immune profile and omic profile.
Study Groups/Cohorts
  • low dose aspirin
    high-risk women given LDA at ≤16 weeks.
    Intervention: Diagnostic Test: Blood test
  • Non responders to low dose aspirin
    high-risk women who have not responded to LDA and have gone on to develop PE.
    Intervention: Diagnostic Test: Blood test
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: July 16, 2021)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 1, 2023
Estimated Primary Completion Date September 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion criteria

  • Age 18-60 years
  • Singleton pregnancy
  • Live fetus at 11-13 weeks of gestation
  • Informed, written consent
  • Upper age of 60 years
  • Patient taking low dose aspirin as standard of care

Exclusion criteria

  • Unwilling or unable to give consent
  • Participants who are unable to understand written English
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT04974892
Other Study ID Numbers IRAS 294761
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Queen Mary University of London
Study Sponsor Queen Mary University of London
Collaborators Not Provided
Investigators Not Provided
PRS Account Queen Mary University of London
Verification Date May 2021