Does ALlopurinol Regress lefT Ventricular Hypertrophy in End Stage REnal Disease: The ALTERED Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 3
- 主要终点
- The primary outcome is to measure if allopurinol, induces a change in Left ventricular Mass Index in patients with ESRD when compared to placebo.
研究概览
简要总结
Kidney patients on dialysis commonly die because of heart disease. One of the biggest problems in their hearts is that the muscle wall of the heart thickens. This makes it less efficient. We found in patients with mild kidney disease that a drug normally used to treat gout (allopurinol) had the remarkable side effect of being able to reduce this thickening of their heart wall. In this new study we aim to find out if this benefit of allopurinol also occurs in severe kidney patients i.e. those on regular dialysis. We also are trying to figure out the best dose of allopurinol to use. To do this we are planning a study where we will recruit patients with kidney disease who are on dialysis. The 1st phase of the trial will be to determine the best dose of allopurinol to use and the second phase will be to do a clinical trial where patients will be randomly allocated to either this optimum dose of allopurinol or a dummy medication (placebo) and will receive one year of treatment. They will have a special scan of the heart using an MRI machine to measure the extent of thickening of their heart muscle before they start on treatment and will have a further MRI scan when their one year treatment finishes.
Phase 1- the dose finding study, will involve 10 patients who will have between 3 and 7 visits to the hospital scheduled around 4 to 17 dialysis sessions. The later study will involve up to 76 patients who will be asked to attend the hospital up to 8 times over a 13 month period.
详细描述
The ALTERED trial is a randomised, double blinded, placebo controlled multi-centre study conducted in NHS Tayside, NHS Ayrshire & Arran & NHS Greater Glasgow & Clyde to compare allopurinol (dose to be confirmed from dose escalation study noted above) at either, 100mg, 200mg, 250mg, 300mg or 350mg to placebo.
Patients will be enrolled in this trial for a period of between 12 to 13 months.
At screening visit an initial history and clinical examination will be performed. Participants will then undergo an echocardiogram to ensure no significant heart failure unless they have had an ECHO in the previous 4 years..Should the participant be eligible for the study they will have a Cardiac Magnetic Resonance Imaging (MRI) scan prior to their baseline (Randomisation) visit. They will also have bloods taken for safety analysis, have a 12 lead ECG done, vital signs recorded and if they agree have 24 hour BP monitoring.
Once the patient is known to be eligible they will return - for the first randomisation, dosing visit at any time up to four weeks after screening. At this randomisation visit post dialysis session, eligible participants will be randomly assigned to either placebo or allopurinol 100mg.
They will continue on allopurinol/placebo 100mg for 2 weeks, with dosing after each dialysis session only. They can have FMD, PWV and PWA measurements taken. All participants will be offered the opportunity to opt in or out of the FMD, PWV and PWA measurements, which are secondary outcome measures only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •aged 18 years or over
- •end stage renal disease (CKD stage 5 eGFR <15ml/min /1.73m2)
- •been on haemodialysis for at least 3 months.
排除标准
- •Known heart failure
- •Left Ventricular Ejection Fraction <45%,
- •active gout
- •severe hepatic disease
- •or on azathioprine, 6 mercaptopurine, theophylline.
- •malignancy or other life threatening diseases,
- •pregnant or lactating women
- •any contraindication to MRI (claustrophobia, metal implants).
- •with a planned (relative) kidney transplant,
- •Patients who have participated in any other clinical trial within the previous 30 days will be excluded.
- •Patients who are unable to give informed consent will also be excluded from this trial.
- •Any other considered by a study physician to be inappropriate for inclusion
研究组 & 干预措施
Placebo
Participants in this arm will be given placebo with the dose appearing to gradually increase weekly as tolerated up to the dose determined in the first phase of the study. The drug dose will be given orally 3 times weekly after dialysis for 1 year.
干预措施: Placebo (for allopurinol) (Drug)
Allopurinol
Participants in this arm will be given allopurinol with the dose gradually increasing weekly as tolerated up to the dose determined in the first phase of the study. The drug dose will be given orally 3 times weekly after dialysis for 1 year.
干预措施: Allopurinol (Drug)
结局指标
主要结局
The primary outcome is to measure if allopurinol, induces a change in Left ventricular Mass Index in patients with ESRD when compared to placebo.
时间窗: following 1 year of therapy
次要结局
- To decide on optimum dosing regime of allopurinol in End Stage Renal Disease from pilot study(6 weeks)
- To assess if the incidence of adverse events differs on allopurinol compared to placebo in patients with end stage renal disease(during course of 1 year of therapy)
- To measure any change in LV end systolic volume, LV end diastolic volume or LV ejection factor with allopurinol in ESRD patients compared with placebo.(Following 1 year of therapy)
- To measure changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo.(Following 1 year of therapy)
- To measure any difference in endothelial function with allopurinol compared with placebo, measured by Flow Mediated Dilatation and Pulse Wave Analysis(following 1 year of therapy)
- To measure changes in BP control as measured by clinic BP and 24hr BP monitoring with allopurinol compared with placebo(Following 1 year of therapy)
研究者
Elaine Rutherford
Clinical Research Fellow - Principal Investigator
University of Dundee