Chronic Thrombo-embolic Pulmonary Hypertension: Classification and Long Term Outcome

Chronic Thromboembolic Pulmonary Hypertension Clinical Trial

Official title:

Chronic Thrombo-embolic Pulmonary Hypertension: Classification and Long Term Outcome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02565030
• Other study ID #: STH18804
• Status: Completed
• Start date: February 2015
• Est. completion date: October 2021

Study information

• Verified date: June 2022
• Source: Sheffield Teaching Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will help to provide more up to date prognostic data on the natural history of untreated proximal CTEPH which will be helpful in discussions regarding surgical versus medical treatment and by exploring the similarities and differences between distal CTEPH and IPAH the investigators hope to get insights into disease mechanisms in patients with distal CTEPH.

Description:

Chronic thrombo-embolic pulmonary hypertension (CTEPH) is thought to represent the consequence of failure of thrombus resolution after the establishment of thrombosis within the elastic pulmonary arteries. Thrombotic material becomes fibrosed, with occlusive vascular remodeling and the development of a secondary small vessel arteriopathy, termed the two-compartment model. This results in an increase in pressure and vascular resistance in the pulmonary vasculature and leads eventually to right heart failure.

It has been demonstrated that 2 year survival for CTEPH patients with mean pulmonary arterial pressure(mPAP) >50 mm Hg was only 20%, however, preliminary data from Sheffield Teaching Hospitals suggest that survival is significantly better than this. Until recently surgery was the only treatment for CTEPH in selected patients. Studies have shown the 10 year survival in patients with CTEPH after PEA surgery was 74%. More recently, for patients with inoperable CTEPH, drug therapy has been shown to improve exercise capacity. Despite recent publications the natural history and mechanisms underlying CTEPH are poorly understood.

The main area of research focus in this study will be improving understanding of the natural history of chronic thromboembolic pulmonary hypertension. The purpose of this research protocol is to conduct a retrospective review of patients with CTEPH diagnosed at the Sheffield Centre between 2001 and 2014 to understand more about the natural history of disease including prognostic indicators. The Sheffield Service has one of the largest cohorts of CTEPH in the world (>650 diagnosed cases since 2001). Approximately half of these patients undergo curative surgery with pulmonary endarterectomy. However, a significant proportion of patients with operable disease decline surgery and a significant proportion of patients have disease that is too distal for surgery, so called distal CTEPH. There is a relative paucity of data on i) the natural history of this disease, ii) an understanding of the relative contribution of obstruction and distal vasculopathy to elevations in pulmonary vascular resistance iii) the effects of distal CTEPH on right ventricular function and iv) how distal CTEPH differs from idiopathic pulmonary arterial hypertension (IPAH).

The second part of this study will focus on understanding disease mechanisms utilising MR imaging techniques and using the Sheffield PH Biobank resource to understand differences in the IPAH and distal CTEPH cohorts. The Sheffield PH Biobank has samples and detailed phenotypic data on over 400 treatment naïve patients with all forms of pulmonary hypertension with serial sampling and long term follow up providing a unique resource to make detailed comparisons across all forms of pulmonary hypertension.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients with the diagnosis of chronic thromboembolic pulmonary hypertension and Idiopathic pulmonary arterial hypertension (as per the European Society of Cardiology guidelines) who presented to Sheffield Pulmonary Vascular Disease Unit at the Royal Hallamshire Hospital between 1st Jan 2001 and 1st Dec 2014.

Exclusion Criteria:

• Patients with Pulmonary Hypertension who have other causes of pulmonary hypertension in addition to chronic thromboembolic pulmonary hypertension and Idiopathic pulmonary arterial hypertension.

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Idiopathic Pulmonary Arterial Hypertension
• Pulmonary Arterial Hypertension

Locations

Country	Name	City	State
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	South Yorkshire

Sponsors (2)

Lead Sponsor	Collaborator
Sheffield Teaching Hospitals NHS Foundation Trust	University of Sheffield

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

Condliffe R, Kiely DG, Gibbs JS, Corris PA, Peacock AJ, Jenkins DP, Goldsmith K, Coghlan JG, Pepke-Zaba J. Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension. Eur Respir J. 2009 Feb;33(2):332-8. doi: 10.1183/09031936.0009 — View Citation

Hurdman J, Condliffe R, Elliot CA, Davies C, Hill C, Wild JM, Capener D, Sephton P, Hamilton N, Armstrong IJ, Billings C, Lawrie A, Sabroe I, Akil M, O'Toole L, Kiely DG. ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a RE — View Citation

J Cannon, K Page, M Roots, A Ponnaberanam, C Tracy, D Taboada Buasso, K Sheares, C Ng, J Dunning, S Tsui, J Pepke-Zaba, D Jenkins.Outcome after Pulmonary Endarterectomy(PEA):Long term followup of UK National Cohort. Thorax 2013;68(Suppl 3):A25-A26.

Pepke-Zaba J, Delcroix M, Lang I, Mayer E, Jansa P, Ambroz D, Treacy C, D'Armini AM, Morsolini M, Snijder R, Bresser P, Torbicki A, Kristensen B, Lewczuk J, Simkova I, Barberà JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Hami — View Citation

Riedel M, Stanek V, Widimsky J, Prerovsky I. Longterm follow-up of patients with pulmonary thromboembolism. Late prognosis and evolution of hemodynamic and respiratory data. Chest. 1982 Feb;81(2):151-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	All patients with CTEPH or IPAH who have been documented as having died between 01/01/2001 and 01/09/2015	Upto 176 months
Secondary	Mean Pulmonary Arterial Pressure(mm of Hg)	Measure of the final Mean Pulmonary Arterial Pressure with Right Heart Catheter studies in patients with CTEPH and IPAH reported between 01/01/2001 and 01/09/2015	Upto 176 months
Secondary	Diffusion across the lung of Carbon Monoxide(mmol/min/KPa)	Measure of final Diffusion across the lung of Carbon Monoxide in patients with CTEPH & IPAH reported between 01/01/2001 and of 01/09/2015	Upto 176 months
Secondary	Emphasis 10 Quality Of Life Questionaire Score(0-50)	Measure of the Emphasis 10 Quality of Life Questionaire Score in patients with CTEPH and IPAH in their final clinic visit reported between 01/01/2001 and 01/09//2015	Upto 176 months
Secondary	Incremental Shuttle Walk Distance( in metres)	The measure of the final Incremental Shuttle Walk Distance of patients with CTEPH and IPAH reported between 01/01/2015 and 01/09/2015	Upto 176 months
Secondary	World Health Organization Functional Class(I-IV)	Measure of the final World Health Organization Functional Class in patients with CTEPH and IPAH reported between 01/01/2001 and 01/09/2015	Upto 176 months
Secondary	Right Ventricular Ejection Fraction(%)	Measure of the final Right Ventricular Ejection Fraction with Cardiac Magnetic Resonance Imaging(MRI) in patients with CTEPH and IPAH reported between 01/01/2001 and 01/09/2015	Upto 176 months