A Prospective Study Comparing the REpeatability and Sensitivity to Change of Non-invasive Endpoints in Pulmonary arterIal hypeRtEnsion
试验速览
- 阶段
- 不适用
- 入组人数
- 44
- 主要终点
- Repeatability of endpoints
研究概览
简要总结
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.
详细描述
Background:
Pulmonary arterial hypertension (PAH) is a rare but severe and progressive disorder, with a prevalence of approximately 50 in 1,000,000 of the population. The condition is incurable with high morbidity and mortality despite the development of effective treatment options. The emergence of goal orientated therapy initially focused interest on prognostic markers that can both inform the clinician regarding disease severity at presentation and be used to follow-up response to therapy and aid in decisions regarding listing for transplantation. A number of effective therapies are available but are very expensive and there is an urgent need for non-invasive and specific markers to assess treatment response and guide therapy. Accurate follow up with reproducible measurements of the heart and pulmonary vasculature are essential in order to accurately characterise treatment response.
Magnetic resonance imaging (MRI) a non-ionising and non-invasive technique provides accurate and reproducible information on cardiac morphology and function. MR imaging is becoming an established technique in the evaluation of patients with PAH, allowing direct visualisation and accurate analysis of the structure and function of the right ventricle (RV). There is a pressing need to validate and standardise MRI methods in pulmonary hypertension to allow clinical translation nationally and internationally and to support trials of novel disease modifying therapies.
Aims:
The aim of this study is to determine the repeatability and capability of detecting change of MR imaging measurements in comparison with walk tests and blood tests in patients with PAH, and define the optimal MRI analysis protocol for use in clinical practice and in future studies in PAH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with PAH
- •Inclusion Criteria:
- •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
排除标准
- •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
- •Inclusion criteria:
- •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.
研究组 & 干预措施
Treatment change patients
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
干预措施: MRI (Device)
Stable patients
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
干预措施: MRI (Device)
Healthy volunteers
MRI 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP
干预措施: MRI (Device)
Treatment naive patients
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
干预措施: MRI (Device)
结局指标
主要结局
Repeatability of endpoints
时间窗: Measurements repeated within 24 hours
Repeatability of MRI, 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP
Sensitivity to change of endpoints
时间窗: Follow up visits performed at 1-12 months
Sensitivity to change of MRI, 6 minute walk test, incremental shuttle walk test, NT-Pro BNP and BNP
次要结局
未报告次要终点
研究者
Andy J Swift
Wellcome Trust Clincial Research Career Development Fellow - principle investigator
University of Sheffield