Iodine Subtraction Mapping in the Diagnosis of Chronic Pulmonary Thromboembolic Disease (INSPIRE)

February 8, 2019 updated by: Andy J Swift, University of Sheffield

IodiNe Subtraction maPpIng in the Diagnosis of chRonic Pulmonary thromboEmbolic Disease (INSPIRE): An Observational Diagnostic Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe but treatable disease that is commonly underdiagnosed. Computed tomography lung subtraction iodine mapping (CT-LSIM) in addition to standard CT pulmonary angiography (CTPA) may improve the evaluation of suspected chronic pulmonary embolism and improve the diagnostic pick up rate. The investigators aim to recruit 100 patients suspected of having CTEPH and perform CT-LSIM scans in addition to the current gold standard test of nuclear medicine test (lung single photon emission computed tomography (SPECT) imaging) as a pilot study which will contribute to and inform the definitive trial. The diagnostic accuracy of CT-LSIM and lung SPECT will be compared. The primary outcome of the full definitive study is non-inferiority of CT-LSIM versus lung SPECT imaging.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable, life-threatening disease that occurs in up to 4% of patients following acute pulmonary embolism (PE)(1). The disease is characterised by remodelling of the pulmonary arteries due to poor clearance of clot. Prognosis is very poor without treatment, and pulmonary endarterectomy (PEA) is well established as the definitive and potentially curative treatment method for CTEPH.

The European Society of Cardiology recommends ventilation/perfusion single photon emission tomography (V/Q SPECT) as the first line-screening test for patients with CTEPH. The perfusion image involves injection of 99mTc labelled macroaggregated human albumin, exposing the patient to ionizing radiation and the study acquisition time is 30-40 minutes.

Evaluation of the pulmonary arterial tree by computed tomography pulmonary angiography (CTPA) and lung perfusion is required to determine the appropriate treatment strategy in chronic thromboembolic disease (CTED). Recently, there has been much interest in the application of lung perfused blood volume images using dual-energy CT (DECT) to assess lung perfusion (2, 3). However, DECT is not widely available in hospitals across the UK and V/Q SPECT remains the reference standard. The rationale, methodology and design of the IodiNe SubtracTion mappInG in the diAgnosis of chronic pulmonary ThromboEmbolic disease (INSTIGATE) study are summarised in this paper.

Rationale of the INSTIGATE study:

Computed tomography lung subtraction iodine mapping (CT-LSIM) and accompanying software is now available in routine clinical practice (Sure subtractionTM, Toshiba Medical Systems; FDA report K130960). CT-LSIM images are created using on a non-rigid registration of a low dose unenhanced thoracic CT to a CTPA, with both examinations performed during the same sitting in less than 10 minutes total scanning time. Subtraction of the non-contrast CT from the contrast-enhance CTPA produces the CT-LSIM. CT-LSIM simultaneously provide high-spatial-resolution images of the pulmonary arterial tree and parenchymal anatomy in combination with functional examination of lung perfusion.

Magnetic resonance imaging (MRI) is an alternative approach with the advantage of the lack of ionizing radiation and can produce lung perfusion maps with good diagnostic accuracy for CTED (5). MRI is relatively limited in comparison to CT in terms of availability and the lack of ability to provide an out of hours service in some centres. Recently, it has been shown that Gadolinium is deposited in the basal ganglia, the clinical significance of the retained gadolinium in the brain, if any, remains unknown (4). Further research is ongoing.

A recent meta-analysis and systematic review, highlights the diagnostic potential of CT in both screening and for surgical and interventional operability (6).

Replacement of CT for V/Q SPECT in the setting of screening for CTED would lead to a cost saving per patient. The diagnosed incidence of CTEPH is approximately 700 cases in the UK, projected to rise to about 1000 in 2025. Estimated pick up rate of perfusion defects in patients with suspected CTED is 59% at a specialist centre (pick up rates are likely to be much lower at non-specialist centres). An estimated 1186 patients are screened at specialist centres, if these patients were screened using CT instead of SPECT, significant cost savings can be made.

In patients found to have CTED on lung SPECT, CTPA is also required to characterise the extent of pulmonary arterial clot for surgical planning, and this would be a further cost. By using CTPA with iodine subtraction mapping for screening and surgical planning.

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

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

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

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patient suspected to have or diagnosed with chronic thromboembolic disease and require a SPECT and CTPA

Description

Inclusion Criteria:

  • Patients suspected to have CTED and require a SPECT and CTPA

Exclusion Criteria:

  • Less than 18 years old
  • Unable to provide informed consent
  • Significant renal dysfunction (GFR <30ml/min)
  • History of hypersensitivity to contrast material
  • Pregnancy

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the diagnostic performance of CT-LSIM for evaluation of pulmonary perfusion in patients with known or suspected chronic thromboembolic pulmonary hypertension (CTEPH)
Time Frame: 12 months
Sensitivity and specificity
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy of CT-LSIM compared with single photon emission computed tomography (SPECT)
Time Frame: 12 months
Sensitivity and specificity
12 months
Diagnostic accuracy of CT-LSIM compared with CT pulmonary angiography (CTPA)
Time Frame: 12 months
Sensitivity and specificity
12 months
Diagnostic accuracy of experienced and less experienced observers
Time Frame: 12 months
Sensitivity and specificity
12 months
Number of alternate diagnoses made on CT-LSIM over lung SPECT imaging
Time Frame: 12 months
Chi square
12 months
Radiation dose between CT-LSIM, SPECT and CTPA
Time Frame: 12 months
Means
12 months

Collaborators and Investigators

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

Sponsor

University of Sheffield

Collaborators

Sheffield Teaching Hospitals NHS Foundation Trust

Investigators

  • Study Director: David Kiely, MD, Sheffield Teaching Hospitals NHS Foundation Trust
  • Study Chair: Yousef Shahin, MD, University of Sheffield
  • Principal Investigator: Andy J Swift, PhD, University of Sheffield
  • Study Chair: Kavitasagary Karunasaagarar, Sheffield Teaching Hospitals NHS Foundation Trust

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 (Anticipated)

April 1, 2019

Primary Completion (Anticipated)

April 1, 2020

Study Completion (Anticipated)

August 30, 2020

Study Registration Dates

First Submitted

January 15, 2019

First Submitted That Met QC Criteria

January 15, 2019

First Posted (Actual)

January 16, 2019

Study Record Updates

Last Update Posted (Actual)

February 12, 2019

Last Update Submitted That Met QC Criteria

February 8, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH20623

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.

Clinical Trials on Chronic Thromboembolic Pulmonary Hypertension

Clinical Trials on Computed tomography lung subtraction iodine mapping

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Dominican Republic

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe