Repeatability and Sensitivity to Change of Non-invasive Endpoints in PAH

NCT03841344 | Unknown

• 1 other identifier: STH18285
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pulmonary arterial hypertension (PAH) is progressive life limiting disease with a median survival of less than 3 years without treatment. Current drug trials in PAH commonly use simple tests for example the 6-minute walk test, blood tests such as N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and BNP, and haemodynamic measures such as PAP and PVR obtained by RHC as endpoints. These tests are surrogate markers of disease severity in patients with pulmonary hypertension. There is now evidence suggesting that magnetic resonance imaging (MRI) may be helpful in the follow up of patients with PAH with high accuracy for the detection of treatment failure, this is because MRI can track changes occurring in the heart by direct visualisation of cardiopulmonary morphology and function, an advantage over existing methods. However, the reproducible of MRI measurements in patients with PAH is not known, and the comparative repeatability of MRI in relation to traditional candidate endpoints such as walk tests and blood tests used in drug trials is not known.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (2)

• Repeatability of endpoints

  Repeatability of MRI, 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP

  Measurements repeated within 24 hours

• Sensitivity to change of endpoints

  Sensitivity to change of MRI, 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP

  Follow up visits performed at 1-12 months

Study Arms (4)

Healthy volunteers

ACTIVE COMPARATOR

MRI 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP

Device: MRI

Treatment naive patients

ACTIVE COMPARATOR

MRI 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP Patients diagnosed with PAH initiating PAH therapy for the first time

Device: MRI

Treatment change patients

ACTIVE COMPARATOR

MRI 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP Patients diagnosed with PAH, currently on PAH therapy who are undergoing an escalation of PAH therapy

Device: MRI

Stable patients

ACTIVE COMPARATOR

MRI 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP Patients with PAH who are NOT undergoing changes in their treatment regime

Device: MRI

Interventions

MRI DEVICE

Evaluation of the utility of candidate endpoints in PAH trials

Also known as: 6 minute walk test, incremental shuttle walk test, NT-ProBNP and BNP

Healthy volunteers; Stable patients; Treatment change patients; Treatment naive patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PAH subject is diagnosed with Group 1 pulmonary arterial hypertension, including IPAH, hereditable and CTD, and PAH associated with portal hypertension
• Mean pulmonary arterial pressure ≥ 25 mmHg
• Pulmonary arterial wedge pressure ≤ 15 mmHg

You may not qualify if:

• Inability to perform the study protocol
• Significant comorbidity where in the opinion of the clinician this is a significant contributor to the patients PAH
• Pregnancy
• Allergy to contrast medium
• Contraindication to MRI (as per standard screening questionnaire)
• Significant lung disease.
• Known Hep B,C, HIV
• Healthy volunteers
• Male or female aged between 18 years and 60 years
• Currently healthy as determined by a responsible physician
• No significant history of lung or cardiac disease and normal BNP.
• Capable of giving written informed consent.
• Subject is \>50kg with a body mass index within the range 18.0 to 32kg/m2.

Sponsors & Collaborators

• University of Sheffield: lead
• GlaxoSmithKline: collaborator

Related Publications (2)

• Alabed S, Alandejani F, Dwivedi K, Karunasaagarar K, Sharkey M, Garg P, de Koning PJH, Toth A, Shahin Y, Johns C, Mamalakis M, Stott S, Capener D, Wood S, Metherall P, Rothman AMK, Condliffe R, Hamilton N, Wild JM, O'Regan DP, Lu H, Kiely DG, van der Geest RJ, Swift AJ. Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction. Radiology. 2022 Oct;305(1):68-79. doi: 10.1148/radiol.212929. Epub 2022 Jun 14.

  PMID: 35699578 DERIVED

• Swift AJ, Wilson F, Cogliano M, Kendall L, Alandejani F, Alabed S, Hughes P, Shahin Y, Saunders L, Oram C, Capener D, Rothman A, Garg P, Johns C, Austin M, Macdonald A, Pickworth J, Hickey P, Condliffe R, Cahn A, Lawrie A, Wild JM, Kiely DG. Repeatability and sensitivity to change of non-invasive end points in PAH: the RESPIRE study. Thorax. 2021 Oct;76(10):1032-1035. doi: 10.1136/thoraxjnl-2020-216078. Epub 2021 Feb 25.

  PMID: 33632769 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Walk Test

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Exercise Test; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Wellcome Trust Clincial Research Career Development Fellow - principle investigator

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 15, 2019
• Study Start: September 15, 2015
• Primary Completion: September 24, 2018
• Study Completion: May 20, 2019
• Last Updated: February 18, 2019

Record last verified: 2019-02