Pulmonary Hypertension, Primary, 4 Clinical Trial
Official title:
Role of Inflammation and Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension
Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by scarred blood clots in the
blood vessels supplying the lungs. This in turn leads to failure of the right side of the
heart. The reason why these scarred clots form is unknown. An operation to remove the scarred
clots, known as pulmonary endarterectomy, is a potential cure. However, some patients have
persistent obstructions within the blood vessels and heart failure even after surgery.
It is thought that abnormal levels of proteins, found in the blood stream and responsible for
inflammation and the development of new blood vessels may have role in causing the disease.
In this study, these proteins were measured to assess whether they provide clues as to the
cause of the disease and whether they could be used for the risk stratification of patients.
Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed form of pulmonary
hypertension whose pathogenesis remains to be fully elucidated. Altered endothelial
homeostasis, defective angiogenesis and inflammation have been implicated. The formation of
the organised occlusions is considered to arise from a failure to resolve acute pulmonary
emboli. There is emerging evidence supporting the role of mediators of angiogenesis,
inflammation and the coagulation cascade (and their many interactions) in CTEPH. Pulmonary
endarterectomy (PEA), to remove these occlusions, may be a cure in some patients. Assessing
circulating proteins associated with these processes may be not only useful for understanding
disease pathogenesis but may also lead to improvements in clinical assessment.
The study was approved by the Regional Ethics Committee (Papworth Hospital Research Tissue
Bank; 08/H0304/56+5). Consecutive patients undergoing PEA surgery at Royal Papworth Hospital
National Health Service Foundation Trust, United Kingdom, who consented for participation in
the Research Tissue Bank between February 2012 and August 2014, were recruited. A validation
data set included all consecutive samples collected from CTEPH patients prior to PEA between
April 2010 and Aug 2017. Patients were diagnosed in accordance with international guidelines.
Patients had serum samples collected from a peripheral vein prior to PEA. In a subset of
patients, further sampling was performed at the first follow up visit to Papworth Hospital
3-6 months post-PEA. Customized human cytokine/chemokine magnetic bead assays and customized
human angiogenesis/growth factor assays were used to measure levels of circulating proteins
in these serum samples (interleukin [IL] 6, IL8, IL10, tumour necrosis factor [TNF] α,
angiopoietin 2 [Ang2], endoglin, vascular endothelial growth factor [VEGF] a, VEGFc, VEGFd
and bone morphogenetic protein 9 [BMP9]).
Levels were compared to levels from patients with chronic thromboembolic disease but no
pulmonary hypertension (CTED) and healthy age and sex matched controls. In addition
multivariate rank regression models were used to assess associations between levels of
circulating proteins and clinical assessments carried out as part of the patients routine
clinical care.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT04808596 -
Pulmonary Hypertension Biorepository and Registry
|
||
| Completed |
NCT03344159 -
Spironolactone Therapy in Chronic Stable Right HF Trial
|
Phase 4 |