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

June 23, 2022 updated by: Sheffield Teaching Hospitals NHS Foundation Trust
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.

Study Overview

Status

Completed

Conditions

Detailed 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.

Study Type

Observational

Enrollment (Actual)

1200

Contacts and Locations

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

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Sheffield Teaching Hospitals NHS Foundation Trust

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients referred to Sheffield Pulmonary Vascular Disease Unit from the Midlands , North of England & Wales.

Description

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.

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

Cohorts and Interventions

Group / Cohort
CTEPH surgical disease, operated
Patients with proximal CTEPH who have undergone Pulmonary Endarterectomy (PEA) surgery
CTEPH surgical disease, not operated

Patients with proximal CTEPH with operable distribution of disease& have not undergone PEA surgery due to the following reasons:

  1. Multiple co-morbidities
  2. Patients choice
  3. Mild disease /symptoms
  4. Awaiting Surgery
CTEPH non surgical
Patients with distal CTEPH with inoperable distribution of disease inaccessable to surgery.
IPAH
Patients with IPAH as per European Society of Cardiology(ESC) criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death
Time Frame: Upto 176 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Pulmonary Arterial Pressure(mm of Hg)
Time Frame: Upto 176 months
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
Diffusion across the lung of Carbon Monoxide(mmol/min/KPa)
Time Frame: Upto 176 months
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
Emphasis 10 Quality Of Life Questionaire Score(0-50)
Time Frame: Upto 176 months
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
Incremental Shuttle Walk Distance( in metres)
Time Frame: Upto 176 months
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
World Health Organization Functional Class(I-IV)
Time Frame: Upto 176 months
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
Right Ventricular Ejection Fraction(%)
Time Frame: Upto 176 months
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

Collaborators and Investigators

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

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

University of Sheffield

Investigators

  • Principal Investigator: Syed Quadery, MBBS, Sheffield Teaching Hospitals NHS Foundation Trust
  • Study Chair: David Kiely, MD, Sheffield Teaching Hospitals NHS Foundation Trust
  • Study Director: Wild Jim, PhD, University Of Sheffield, School of Medicine
  • Study Director: Andy Swift, MD, University Of Sheffield , School Of Medicine

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 (ACTUAL)

February 1, 2015

Primary Completion (ACTUAL)

October 1, 2021

Study Completion (ACTUAL)

October 1, 2021

Study Registration Dates

First Submitted

September 28, 2015

First Submitted That Met QC Criteria

September 29, 2015

First Posted (ESTIMATE)

October 1, 2015

Study Record Updates

Last Update Posted (ACTUAL)

June 24, 2022

Last Update Submitted That Met QC Criteria

June 23, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH18804

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.

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