NCT06048458

Brief Summary

Observational prospective cohort study designed to assess the mechanisms of fluoropyrimidine induced cardiovascular toxicity.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
75

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started May 2022

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2022

Completed
21 days until next milestone

Study Start

First participant enrolled

May 18, 2022

Completed
1.3 years until next milestone

First Posted

Study publicly available on registry

September 21, 2023

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2023

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2024

Completed
Last Updated

September 21, 2023

Status Verified

December 1, 2022

Enrollment Period

1.5 years

First QC Date

April 27, 2022

Last Update Submit

September 15, 2023

Conditions

Cardiovascular DiseasesCardiotoxicityFluorouracil Adverse ReactionMalignancyColorectal CancerOesophagus CancerGastric CancerPancreatic Cancer

Keywords

Cardio-oncologyCardiotoxicityFluoropyrimidine cardiotoxicity

Outcome Measures

Primary Outcomes (1)

  • Change in myocardial blood flow from baseline with adenosine stress assessed by quantitative perfusion cardiac MRI

    Assessed at baseline, following cycle 1 and 4-6 weeks post completion of treatment

    6 months

Secondary Outcomes (8)

  • Change in left ventricular ejection fraction from baseline

    6 months

  • Change in left ventricular extracellular volume from baseline

    6 months

  • Change in left ventricular global longitudinal strain from baseline

    6 months

  • Change in N-terminal pro B-type natriuretic peptide (NT-pro BNP)

    6 months

  • Change in high sensitivity troponin T

    6 months

  • +3 more secondary outcomes

Study Arms (2)

Cohort 1

Stable patients with gastrointestinal malignancies will be recruited to this 3 timepoint study prior to initiation of fluoropyrimidine chemotherapy. All investigations will be performed at baseline, at the end of cycle 1 and 4-6 weeks post completion of treatment.

Diagnostic Test: Cardiovascular magnetic resonance with stress perfusionDiagnostic Test: CT coronary angiographyDiagnostic Test: Retinal OCT angiographyDiagnostic Test: Sublingual microscopy (GlycoCheck)Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Cohort 2

Patients with gastrointestinal malignancies presenting to hospital with acute symptoms of fluoropyrimidine cardiotoxicity. All investigations will be performed during the acute presentation and the second visit will be performed 4-6 weeks post completion of treatment.

Diagnostic Test: Cardiovascular magnetic resonance with stress perfusionDiagnostic Test: CT coronary angiographyDiagnostic Test: Retinal OCT angiographyDiagnostic Test: Sublingual microscopy (GlycoCheck)Diagnostic Test: Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)

Interventions

Cardiovascular magnetic resonance with stress perfusionDIAGNOSTIC_TEST

Cardiac MRI scan to assess changes in left ventricular function, parametric mapping, strain and myocardial blood flow. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Cohort 1Cohort 2
CT coronary angiographyDIAGNOSTIC_TEST

CT coronary angiogram at baseline only in both cohorts to assess for coronary artery disease

Cohort 1Cohort 2
Retinal OCT angiographyDIAGNOSTIC_TEST

Retinal OCTa to assess changes in retinal vasculature. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Cohort 1Cohort 2
Sublingual microscopy (GlycoCheck)DIAGNOSTIC_TEST

To determine changes in sublingual microvascular health. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Cohort 1Cohort 2
Serum cardiac biomarkers (High sensitivity troponin, NT pro BNP)DIAGNOSTIC_TEST

Performed to assess for myocardial injury. In cohort 1 this will be performed pre, during and on completion of treatment. In cohort 2 this will be performed during the acute presentation and on completion of treatment.

Cohort 1Cohort 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Adult patients with gastrointestinal malignancies being treated with a fluoropyrimidine based chemotherapy regimen.

You may qualify if:

  • Age \>18 years
  • Gastrointestinal malignancy
  • Receiving fluoropyrimidine chemotherapy

You may not qualify if:

  • Participants unable or unwilling to provide consent
  • Participants that have a conventional contraindication for magnetic resonance imaging (MRI) including permanent implantable cardiac devices, ferromagnetic implants, pregnancy, large body size not fitting into the scanner bore and severe claustrophobia will be excluded
  • Participants that have a conventional contraindication for adenosine stress perfusion including a history of trifascicular block or of second-degree heart block or higher on ECG, or uncontrolled asthma.
  • Participants with significant renal impairment (eGFR\<30ml/min)
  • History of allergy to adenosine, gadolinium or iodinated contrast
  • Patients with terminal illness (life expectancy \<6 months) will be excluded.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St Bartholomews Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

MeSH Terms

Conditions

Cardiovascular DiseasesCardiotoxicityNeoplasmsColorectal NeoplasmsEsophageal NeoplasmsStomach NeoplasmsPancreatic Neoplasms

Condition Hierarchy (Ancestors)

Heart DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and InjuriesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesHead and Neck NeoplasmsEsophageal DiseasesStomach DiseasesEndocrine Gland NeoplasmsPancreatic DiseasesEndocrine System Diseases

Study Officials

  • Charlotte Manisty, PhD

    UCL

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Aderonke Abiodun, MBChB

CONTACT

02073777000aderonketemilade.abiodun@nhs.net

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2022

First Posted

September 21, 2023

Study Start

May 18, 2022

Primary Completion

December 1, 2023

Study Completion

February 1, 2024

Last Updated

September 21, 2023

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)