Chronic Thromboembolic Pulmonary HypertensionINSPIRENCT03806907
Iodine Subtraction Mapping in the Diagnosis of Chronic Pulmonary Thromboembolic Disease
An observational study of Chronic Thromboembolic Pulmonary Hypertension, run by University of Sheffield.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension
- What is being tested?
- Computed tomography lung subtraction iodine mapping
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2019to 30 Aug 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Adult, Older adult
Study population: Patient suspected to have or diagnosed with chronic thromboembolic disease and require a SPECT and CTPA
Who may be able to join
- Patients suspected to have CTED and require a SPECT and CTPA
Who cannot join
- Less than 18 years old
- Unable to provide informed consent
- Significant renal dysfunction (GFR <30ml/min)
- History of hypersensitivity to contrast material
- Pregnancy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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.
Read the 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.
- Being tested
- Computed tomography lung subtraction iodine mapping
- Keywords
- INSITIGATE, Pulmonary Hypertension, Pulmonary embolism, Chronic Thromboembolism, Iodine Subtraction
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Computed tomography lung subtraction iodine mappingRadiation
Also called CT-LSIM
Subtraction of the non-contrast CT from the contrast-enhance CTPA produces the CT-LSIM
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the diagnostic performance of CT-LSIM for evaluation of pulmonary perfusion in patients with known or suspected chronic thromboembolic pulmonary hypertension (CTEPH)
Sensitivity and specificity
Measured: 12 months
Secondary outcomes (5)
Diagnostic accuracy of CT-LSIM compared with single photon emission computed tomography (SPECT)
Sensitivity and specificity
Measured: 12 months
Diagnostic accuracy of CT-LSIM compared with CT pulmonary angiography (CTPA)
Sensitivity and specificity
Measured: 12 months
Diagnostic accuracy of experienced and less experienced observers
Sensitivity and specificity
Measured: 12 months
Number of alternate diagnoses made on CT-LSIM over lung SPECT imaging
Chi square
Measured: 12 months
Radiation dose between CT-LSIM, SPECT and CTPA
Means
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2019
- Study start1 Apr 2019 (estimated)
- Primary completion1 Apr 2020 (estimated)
- Study completion30 Aug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sheffield
- Sponsor type
- University, hospital or other
- Collaborators
- Sheffield Teaching Hospitals NHS Foundation Trust
- Responsible party
- Principal investigator, Andy J Swift, University of Sheffield
- Investigators
- David Kiely, MD, Study director, Sheffield Teaching Hospitals NHS Foundation TrustYousef Shahin, MD, Study chair, University of SheffieldAndy J Swift, PhD, Principal investigator, University of SheffieldKavitasagary Karunasaagarar, Study chair, Sheffield Teaching Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03806907
- Sponsor's protocol ID
- STH20623
- Acronym
- INSPIRE
- Status last verified
- Feb 2019
- First submitted
- 15 Jan 2019
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004 May 27;350(22):2257-64. doi: 10.1056/NEJMoa032274.
PubMed 15163775Hoey ET, Gopalan D, Ganesh V, Agrawal SK, Qureshi N, Tasker AD, Clements L, Screaton NJ. Dual-energy CT pulmonary angiography: a novel technique for assessing acute and chronic pulmonary thromboembolism. Clin Radiol. 2009 Apr;64(4):414-9. doi: 10.1016/j.crad.2008.11.007. Epub 2009 Jan 14. No abstract available.
PubMed 19264187Hoey ET, Mirsadraee S, Pepke-Zaba J, Jenkins DP, Gopalan D, Screaton NJ. Dual-energy CT angiography for assessment of regional pulmonary perfusion in patients with chronic thromboembolic pulmonary hypertension: initial experience. AJR Am J Roentgenol. 2011 Mar;196(3):524-32. doi: 10.2214/AJR.10.4842.
PubMed 21343493Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB; International Society for Magnetic Resonance in Medicine. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017 Jul;16(7):564-570. doi: 10.1016/S1474-4422(17)30158-8. Epub 2017 Jun 13.
PubMed 28653648Rajaram S, Swift AJ, Capener D, Telfer A, Davies C, Hill C, Condliffe R, Elliot C, Hurdman J, Kiely DG, Wild JM. Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension. Eur Radiol. 2012 Feb;22(2):310-7. doi: 10.1007/s00330-011-2252-x. Epub 2011 Sep 2.
PubMed 21887483Dong C, Zhou M, Liu D, Long X, Guo T, Kong X. Diagnostic accuracy of computed tomography for chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis. PLoS One. 2015 Apr 29;10(4):e0126985. doi: 10.1371/journal.pone.0126985. eCollection 2015.
PubMed 25923810
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IodiNe Subtraction maPpIng in the Diagnosis of chRonic Pulmonary thromboEmbolic Disease (INSPIRE): An Observational Diagnostic Study
- ClinicalTrials.gov ID
- NCT03806907
- Acronym / sponsor ID
- INSPIRE / STH20623
- Keywords
- INSITIGATE, Pulmonary Hypertension, Pulmonary embolism, Chronic Thromboembolism, Iodine Subtraction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of SheffieldUniversity, hospital or other
- Collaborators
- Sheffield Teaching Hospitals NHS Foundation Trust
- Study start
- 1 Apr 2019 (estimated)
- Primary completion
- 1 Apr 2020 (estimated)
- Study completion
- 30 Aug 2020 (estimated)
- First posted
- 16 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patient suspected to have or diagnosed with chronic thromboembolic disease and require a SPECT and CTPA
Key inclusion criteria (1 listed)
- Patients suspected to have CTED and require a SPECT and CTPA
Key exclusion criteria (5 listed)
- Less than 18 years old
- Unable to provide informed consent
- Significant renal dysfunction (GFR <30ml/min)
- History of hypersensitivity to contrast material
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Computed tomography lung subtraction iodine mappingAlso: CT-LSIMSubtraction of the non-contrast CT from the contrast-enhance CTPA produces the CT-LSIM | Radiation | – |
Primary outcome
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
5 secondary outcomes
Diagnostic accuracy of CT-LSIM compared with single photon emission computed tomography (SPECT)
Time frame: 12 months
Diagnostic accuracy of CT-LSIM compared with CT pulmonary angiography (CTPA)
Time frame: 12 months
Diagnostic accuracy of experienced and less experienced observers
Time frame: 12 months
Number of alternate diagnoses made on CT-LSIM over lung SPECT imaging
Time frame: 12 months
Radiation dose between CT-LSIM, SPECT and CTPA
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Background: PubMed 15163775Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004 May 27;350(22):2257-64. doi: 10.1056/NEJMoa032274.
- Background: PubMed 19264187Hoey ET, Gopalan D, Ganesh V, Agrawal SK, Qureshi N, Tasker AD, Clements L, Screaton NJ. Dual-energy CT pulmonary angiography: a novel technique for assessing acute and chronic pulmonary thromboembolism. Clin Radiol. 2009 Apr;64(4):414-9. doi: 10.1016/j.crad.2008.11.007. Epub 2009 Jan 14. No abstract available.
- Background: PubMed 21343493Hoey ET, Mirsadraee S, Pepke-Zaba J, Jenkins DP, Gopalan D, Screaton NJ. Dual-energy CT angiography for assessment of regional pulmonary perfusion in patients with chronic thromboembolic pulmonary hypertension: initial experience. AJR Am J Roentgenol. 2011 Mar;196(3):524-32. doi: 10.2214/AJR.10.4842.
- Background: PubMed 28653648Gulani V, Calamante F, Shellock FG, Kanal E, Reeder SB; International Society for Magnetic Resonance in Medicine. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol. 2017 Jul;16(7):564-570. doi: 10.1016/S1474-4422(17)30158-8. Epub 2017 Jun 13.
- Background: PubMed 21887483Rajaram S, Swift AJ, Capener D, Telfer A, Davies C, Hill C, Condliffe R, Elliot C, Hurdman J, Kiely DG, Wild JM. Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR imaging compared with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension. Eur Radiol. 2012 Feb;22(2):310-7. doi: 10.1007/s00330-011-2252-x. Epub 2011 Sep 2.
- Background: PubMed 25923810Dong C, Zhou M, Liu D, Long X, Guo T, Kong X. Diagnostic accuracy of computed tomography for chronic thromboembolic pulmonary hypertension: a systematic review and meta-analysis. PLoS One. 2015 Apr 29;10(4):e0126985. doi: 10.1371/journal.pone.0126985. eCollection 2015.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Kiely, MD study director
Sheffield Teaching Hospitals NHS Foundation Trust
Yousef Shahin, MD study chair
University of Sheffield
Andy J Swift, PhD principal investigator
University of Sheffield
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Thromboembolic Pulmonary Hypertension, run by University of Sheffield.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andy J Swift, PhD (0114 2159595, a.j.swift@sheffield.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03806907, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.