Characterising Pressure-derived Right Ventricular Afterload Indices During Lung Resection Surgery - a Feasibility Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 15
- 主要终点
- Proportion of patients for whom meaningful haemodynamic data is obtained at clinically relevant timepoints
研究概览
简要总结
Lung cancer is a leading cause of cancer death in Scotland and the UK. Surgery, typically using a keyhole approach, provides the best chance of cure. Golden Jubilee National Hospital performs over 600 operations each year, making this the busiest lung surgery department in the country. Unfortunately, some patients suffer disabling breathlessness and a limited ability to perform even very gentle exercise after surgery, even if they had no breathing problems before surgery. Understanding the causes and preventing this breathlessness is the focus of this research.
Despite advances in techniques, lung cancer surgery can result in long-term weakening of the muscular chamber of the right (-hand side of the) heart which pumps blood to the lungs. During surgery, the pressure against which this pump works increases, making it more difficult to push blood into the lungs.
Even after surgery, when the pressure returns to normal, the right heart can remain weak. This weakening can contribute to breathlessness and exercise limitation. Preventing or reducing this right heart weakening may improve quality of life after surgery.
The investigators are interested in understanding why this weakening occurs after lung surgery and then to develop treatments to prevent it. The answer may lie in reversing the high resistance against which the heart pumps during surgery. Ultimately, the aim is to improve patients' recovery from surgery and improve both breathing and the ability to exercise. This problem may be treatable with existing drugs which are proven to be safe, easy to deliver and are already available. These drugs can be given around the time of surgery.
This study will not involve administering new treatments, though future clinical trial(s) are anticipated. Participants' care will be the same as is usually provided. Participants taking part will undergo more tests and monitoring than usual to help understand the changes taking place during and after surgery.
Before a drug trial to test this idea, there are some key things to clarify . This study plans to recruit 15 participants having keyhole lung cancer surgery. The following will be performed:
- Blood Tests: blood samples before and after surgery to check for heart injury.
- Heart monitoring: temporarily insert a thin tube called a right heart catheter into a large blood vessel in the participants' neck the morning of surgery. This will allow continuous measurement of the pressure in the right heart and lung blood vessels. This will help design and deliver treatments, and how best to measure the effects. This heart catheter will be removed the day after surgery.
- Heart scans: perform magnetic resonance imaging (MRI) scans before and after surgery to measure blood flow and examine the impact of surgery on the heart.
详细描述
The investigators hypothesise that a transient, acute rise in right ventricular (RV) afterload occurring during lung resection surgery triggers a sterile inflammatory RV injury resulting in persistent RV dysfunction - even in the absence of sustained postoperative pulmonary vascular resistance - which contributes to disabling postoperative dyspnoea and exercise limitation.
Therapeutic pulmonary vasodilation is a mainstay of treatment to reduce RV afterload and improve V/Q matching in complex conditions such as pulmonary hypertension, thoracic organ transplant, respiratory distress syndromes and congenital cardiac disease, with well-established safety and feasibility profiles. Anti-inflammatory and cytoprotective properties have also been demonstrated. The inhaled route provides systemic and renovascular stability, ease of administration, selective targeting of the pulmonary vasculature, with high bioavailability and a short half-life. Unlike traditional approaches focussing on PH management, the application of IPVs for postoperative RV dysfunction may simultaneously address both contractility and afterload reduction.
Perioperative inhaled pulmonary vasodilator (IPV) therapy may prove to protect the RV from the relatively homogenous insult occurring in controlled clinical conditions as described above. Prior to clinical trials of IPVs, it is necessary to first demonstrate the feasibility of continuous RV / pulmonary vascular haemodynamic perioperative monitoring in lung resection, understand the time course of the perioperative afterload insult and characterise pulmonary vasoreactivity. This study seeks to characterise intraoperative haemodynamics, demonstrating feasibility and inform power calculation for a future early phase IPV trial in lung resection patients.
Aims
Perform a pragmatic single-centre, prospective study of adults undergoing elective lung resection by VATS and RATS to:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presumed or confirmed non-small cell lung cancer
- •Planned (elective) minimally invasive (VATS/RATS) lobectomy using OLV
- •Able to provide informed consent
排除标准
- •Pulmonary / RV physiological: Severe right sided valvular (tricuspid, pulmonary) disease, Preoperative atrial fibrillation / flutter / non-controlled tachydysrhythmia, Severe RA/RV dilatation, Severe PH (mPAP >55mmHg).
- •Awake RHC contraindicated: Severe coagulopathy (PTr >1.5, PTTr >1.5), Thrombocytopenia (<50x109/L), Abnormal vasculature, Unable to lie supine and head down, Endocarditis or intra-cardiac tumour or thrombus, Right-sided valve prosthesis or other implanted cardiac device (e.g. pacing wire), Skin/soft tissue infection overlying insertion point.
- •CMR contraindicated: Severe claustrophobia/unable to lie supine, Class III obesity (BMI >40), Presence of non-MRI compatible foreign body or implanted device.
- •Gadolinium contrast contraindicated: CMR contraindicated (as above) and/or: Intravenous (IV) contrast (Gadolinium) allergy, Acute or chronic renal failure (eGFR <59ml/min).
- •Surgical / medical: Planned sub-lobar resection / wedge resection / isolated middle lobectomy / segmentectomy / pneumonectomy, Planned secondary procedure (e.g. mediastinal/cardiac), Pregnancy.
- •Research: Ongoing participation in other investigational research which would undermine the scientific basis of this study.
结局指标
主要结局
Proportion of patients for whom meaningful haemodynamic data is obtained at clinically relevant timepoints
时间窗: 24 hours
Time per patient from initiation of right heart catheter (RHC)-derived continuous cardiac output (CCO) monitoring to planned postoperative RHC removal that high-quality\* RV/pulmonary haemodynamic data is obtained: \*High quality defined as: ≥80% of patients (≥12/15) in whom ≥80% of planned time point measurements can be obtained for the duration of the planned (24 hour) CCO monitoring window. Proportion of planned time per patient in which RHC provides any CCO monitoring for the duration of the planned (24 hour) CCO monitoring window. Number of patients in whom RHC dislodged and/or premature removal required.
次要结局
- Haemodynamic 1: PVR vs time(24 hours)
- Haemodynamic 2: RHC-derived vs. CMR-derived pulmonary artery flow(24 hours)
- Vasoreactivity(24 hours)
- Cardiac biomarker 1: BNP(48 hours)
- Cardiac biomarker 2: HsTn(48 hours)
- Clinical indicator 1: Length of stay(30 days)
- Clinical indicator 2: Mortality(30 days)
- Clinical indicator 3: Unplanned hospital readmission (all cause)(30 days)
- Validated patient-reported outcome: quality of recovery(48 hours)
- Postoperative complications at 30 days: highest Clavien-Dindo score(30 days)
研究者
Dr Ben Shelley
Honorary Professor
University of Glasgow