Efficacy and Safety of Paclitaxel-Coated Balloon Angioplasty for Dysfunctional Arteriovenous Fistulas: A Multicenter Randomized Controlled Trial
Yanqi Yin, Yaxue Shi, Tianlei Cui, Hua Li, Jianghua Chen, Lihong Zhang, Zhengya Yu, Hong Li, Yan Yan, Kun Wu, and Qizhuang Jin
Rationale & Objective:
Previous studies have illustrated the potential superiority of drug-coated balloons (DCBs) in maintaining patency after initial angioplasty for arteriovenous fistula (AVF) dysfunction due to stenosis. Our trial evaluated the efficacy and safety of DCBs for preventing fistula restenosis in Chinese hemodialysis patients.
Study Design:
Multicenter, prospective, randomized, open-label, blinded end point,controlled trial.
Settings & Participants:
A total of 161 hemodialysis patients with fistula dysfunction from 10 centers in China.
The sample size was calculated based on previous studies with clinically significant end points.
Intervention:
Participants were randomized 1:1 to treatment with initial dilation followed by DCB angioplasty or conventional high-pressure balloon (HPB) angioplasty.
Outcomes: The primary end point was target lesion primary patency defined as the target lesion intervention-free survival in conjunction with an ultrasonography-measured peak systolic velocity ratio (PSVR) ≤2.0 at 6 months. The secondary end points included 1) device, technical, clinical, and procedural success; 2) major adverse events; 3) degree of target lesion stenosis at 6 months; and 4) clinically driven target lesion and target shunt revascularization within 12 months.
Trial Registration:
Registered at Clinical-Trials.gov with study number NCT02962141.
Patient Population Consecutive adult patients with fistula dysfunction who were candidates for PTA therapy (potential ≥50% venous stenosis measured by diagnostic ultrasonography) were further assessed according to the eligibility criteria. Once a patient was recruited as a participant, a baseline evaluation was obtained to record demographic characteristics, medical history, and drug treatment.
Previous studies have illustrated the potential superiority of drug-coated balloons (DCBs) in maintaining patency after initial angioplasty for arteriovenous fistula (AVF) dysfunction due to stenosis. Our trial evaluated the efficacy and safety of DCBs for preventing fistula restenosis in Chinese hemodialysis patients.
Study Design:
Multicenter, prospective, randomized, open-label, blinded end point,controlled trial.
Settings & Participants:
A total of 161 hemodialysis patients with fistula dysfunction from 10 centers in China.
The sample size was calculated based on previous studies with clinically significant end points.
Intervention:
Participants were randomized 1:1 to treatment with initial dilation followed by DCB angioplasty or conventional high-pressure balloon (HPB) angioplasty.
Outcomes: The primary end point was target lesion primary patency defined as the target lesion intervention-free survival in conjunction with an ultrasonography-measured peak systolic velocity ratio (PSVR) ≤2.0 at 6 months. The secondary end points included 1) device, technical, clinical, and procedural success; 2) major adverse events; 3) degree of target lesion stenosis at 6 months; and 4) clinically driven target lesion and target shunt revascularization within 12 months.
Trial Registration:
Registered at Clinical-Trials.gov with study number NCT02962141.
Patient Population Consecutive adult patients with fistula dysfunction who were candidates for PTA therapy (potential ≥50% venous stenosis measured by diagnostic ultrasonography) were further assessed according to the eligibility criteria. Once a patient was recruited as a participant, a baseline evaluation was obtained to record demographic characteristics, medical history, and drug treatment.
Study Devices and Treatment
The Aperto paclitaxel*-coated DCB uses a dose of 3.0 μg/ mm2. Ohicho II HPBs (rated burst pressure, 20-22 atm; Kaneka Corp) were used for initial dilation in both the trial group and the control group.
In the DCB group technically successful initial dilation at the target lesion was required and was followed by DCB treatment with a persistent dilated period of 120 to 180 seconds.
* paclitaxel coating significantly reduces neointimal hyperplasia, the primary cause of hemodialysis access dysfunction and recurrent stenosis after initial angioplasty
Patient Follow-Up
Target lesion and target fistula clinical assessments were performed by experienced nephrologists or vascular surgeons at 1, 3, 6, and 12 months post procedure.
Outcome Measures
The primary end point of the study was target lesion primary patency at 6 months post procedure. Primary patency was defined as target lesion intervention-free survival in conjunction with a DUS-derived peak systolic velocity ratio (PSVR) ≤2.0.
Secondary end points consisted of: (1) device success;(2) technical success; (3) clinical success; (4) procedural success; (5) major adverse events, including death and stroke; (6) the degree of target lesion stenosis at 6 months; (7) clinically driven target lesion revascularization (CDTLR); and (8) clinically driven target shunt revascularization (CD-TSR).
Statistical Analysis
The sample size was calculated based on the primary end point using an expected event rate of 70% and 45% in the DCB and control groups, respectively. 9,19 With the principle of efficient design and an assumed 25% rate of loss to follow up, 160 patients would be necessary for 80% power to detect superiority of DCB to conventional HPB angioplasty at an α level of 0.05.
The Aperto paclitaxel*-coated DCB uses a dose of 3.0 μg/ mm2. Ohicho II HPBs (rated burst pressure, 20-22 atm; Kaneka Corp) were used for initial dilation in both the trial group and the control group.
In the DCB group technically successful initial dilation at the target lesion was required and was followed by DCB treatment with a persistent dilated period of 120 to 180 seconds.
* paclitaxel coating significantly reduces neointimal hyperplasia, the primary cause of hemodialysis access dysfunction and recurrent stenosis after initial angioplasty
Patient Follow-Up
Target lesion and target fistula clinical assessments were performed by experienced nephrologists or vascular surgeons at 1, 3, 6, and 12 months post procedure.
Outcome Measures
The primary end point of the study was target lesion primary patency at 6 months post procedure. Primary patency was defined as target lesion intervention-free survival in conjunction with a DUS-derived peak systolic velocity ratio (PSVR) ≤2.0.
Secondary end points consisted of: (1) device success;(2) technical success; (3) clinical success; (4) procedural success; (5) major adverse events, including death and stroke; (6) the degree of target lesion stenosis at 6 months; (7) clinically driven target lesion revascularization (CDTLR); and (8) clinically driven target shunt revascularization (CD-TSR).
Statistical Analysis
The sample size was calculated based on the primary end point using an expected event rate of 70% and 45% in the DCB and control groups, respectively. 9,19 With the principle of efficient design and an assumed 25% rate of loss to follow up, 160 patients would be necessary for 80% power to detect superiority of DCB to conventional HPB angioplasty at an α level of 0.05.
Results
Study Participants and Procedural Characteristics
The study enrolled 161 participants, including 78 assigned to the DCB group and 83 assigned to the control group, at 10 centers in China from November 2016 to July 2017.
Target Lesion and Fistula Survival
At 6 months post procedure, the percentage with target lesion primary patency as defined by a PSVR ≤2.0 in the DCB group was significantly superior to that in the control group (65% vs 37%; RD [the patency rate in the DCB group minus that in the control group] 28% [95% CI, 13%-43%]; P < 0.001). See blow:
Figure 3: Follow up at 12 moths. DCB superior to HPB.
During DCB angioplasty, paclitaxel infiltrates the vessel walls in contact with the balloon, affecting local vascular endothelial cells with trace dosages leaked into the bloodstream.
Similar safety profiles have been drawn from other studies in which paclitaxel-coated balloons were used for the same indication. The shellac-ammonium salt-based (SAFEPAX Technology) coating of the DCB is thought to reduce drug and excipient loss in the route from the sheath to the target lesion.
Conclusions
Compared to conventional HPB angioplasty, DCB treatment achieved superior primary patency defined using PSVR measured at 6 months and superior intervention-free survival of both the target lesion and the target shunt at 12 months without evidence of greater adverse events
For more information Follow: https://www.ajkd.org/article/S0272-6386(20)31202-6/fulltext
Conclusions
Compared to conventional HPB angioplasty, DCB treatment achieved superior primary patency defined using PSVR measured at 6 months and superior intervention-free survival of both the target lesion and the target shunt at 12 months without evidence of greater adverse events
For more information Follow: https://www.ajkd.org/article/S0272-6386(20)31202-6/fulltext
