High-intensity Atorvastatin for Arteriovenous Fistula Failure (HAFF): A Feasibility Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Patient recruitment rate (in percent)
研究概览
简要总结
Primary failure is the most common complication of newly created arteriovenous fistulas (AVFs) and an important contributor to end stage renal disease (ESRD) patients' morbidity and mortality. Recently, the investigators have found that high intensity atorvastatin (40 mg/day) reduces AVF primary failure significantly when compared to other statins or no statin treatment in three separate prospective and retrospective studies done in collaboration with the University of Miami. Based on these findings and considering the necessity for a therapy to improve AVF maturation rates, the investigators propose the realization of a feasibility pilot double blinded randomized controlled trial (RCT). In this study, a total of 50 patients will be randomly allocated to receive high intensity atorvastatin (40 mg daily) or placebo starting at two weeks before surgery and until the end of the observational period (6 weeks after surgery). Present trial will reveal crucial feasibility information such as the appropriateness of the eligibility criteria, patient recruitment and retention rates, compliance, adverse events, efficacy of patient follow-ups, and readiness of the facilities and involved personnel; while having as a secondary endpoint the predictive measurements of diameter and AVF blood flow 6 weeks after fistula creation useful for the estimation of the probable effect of proposed intervention. Here, the investigators aim to pave the way for a future multicenter Phase II RCT seeking to prove the efficacy of atorvastatin therapy as a perioperative intervention to reduce AVF primary failure.
详细描述
STUDY BACKGROUND AND PURPOSE. Approximately, 30-50% of newly created arteriovenous fistulas (AVF) never mature independently to support hemodialysis, leading to salvage interventions or abandonment of the fistula and creation of a new dialysis access. Failed AVFs are thus associated with increased morbidity, mortality and health care expenditures.
Only two published studies have assessed the effect of statins on AVF primary failure, with contrasting results. Pisoni et al. concluded that statins did not improve AVF maturation, using a retrospective analysis of 317 patients and pooling all statins together as a drug class. Unfortunately, this approach overlooks the potential pleiotropic effects of distinct drugs on AVF remodeling. Overcoming the limitations of Pisoni et al.'s study, the investigators recently published a manuscript evaluating the benefits of three different statins (atorvastatin, rosuvastatin and simvastatin) on AVF outcomes using a retrospective analysis of 535 patients. In this work done in collaboration with the University of Miami, the investigators found a highly statistical significant risk reduction (76%, odds ratio [OR] 0.18, p=0.005) of AVF primary failure by atorvastatin. No other statins significantly improved AVF maturation in this cohort. Interestingly, this study showed that atorvastatin is particularly beneficial for one-stage AVF (96% risk reduction, OR 0.03, p=0.005) and, that higher doses of the drug are associated with lower rates of primary failure in one-stage fistulas. Two more studies done by the same group, a prospective and another retrospective, also support this finding indicating that the use of statins prior to fistula creation is beneficial for the unassisted survival of the AVF.
Compared to other statins, atorvastatin has a distinctive physicochemical and pharmacokinetic profile. These characteristics could explain the differential pleiotropic action of atorvastatin in investigators' study, and why it is superior to its counterparts in improving vascular remodeling after AVF creation.
Based on above findings, the investigators propose a pilot clinical trial to evaluate the feasibility of a study involving ESRD patients undergoing AVF surgery at AMC. Indeed, the investigators long-term goal is the realization of a large multicenter Phase II Randomized Controlled Trial (RCT) to test the efficacy of atorvastatin as a safe and inexpensive therapeutic intervention for the reduction of AVF primary failure.
The present proposal will be implemented as presented in the following specific aim (SA): Evaluate the feasibility of performing a RCT with patients taking atorvastatin and undergoing AVF surgery at Albany Medical College.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age>18 years of age;
- •stage 4 or 5 CKD;
- •one-stage AVF surgery is planned (radiocephalic or brachiocephalic);
- •and statin-naïve or at least 6 months from last statin use.
排除标准
- •revision of an existing AVF instead of a de novo access;
- •known intolerance or hypersensitivity to statins;
- •active liver disease;
- •elevation in AST, ALT or CPK of more than 3 times the upper limit of normal;
- •baseline LDL<40 mg/dL;
- •coadministration of strong interacting drugs;
- •any condition in which statins are contraindicated;
- •involvement in another trial where the intervention may confound the outcome of this trial.
研究组 & 干预措施
Placebo
1 tablet once daily orally for 8 weeks starting 2 weeks before AVF creation
干预措施: Placebo (Other)
Treatment
Atorvastatin 40mg once daily orally for 8 weeks starting 2 weeks before AVF creation
干预措施: Atorvastatin 40mg (Drug)
结局指标
主要结局
Patient recruitment rate (in percent)
时间窗: 104 weeks
The patient recruitment rate (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.
Patient retention rate (in percent)
时间窗: 104 weeks
The patient retention rate (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.
Patient compliance (in percent)
时间窗: 104 weeks
The patient compliance (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.
Rate of adverse events (in percent)
时间窗: 104 weeks
The rate of adverse events (in percent) is an important parameter to evaluate the safety of the study and it is important to plan future Phase II trials.
次要结局
- Ultrasonographic measurement of AVF blood flow (in milliliter per minute).(104 weeks)
- Ultrasonographic measurements of diameter (in millimeters).(104 weeks)
研究者
Loay Salman, MD
Professor of Medicine
Albany Medical College