Clinical trial NCT06034691: Exploratory Research of PCSK9 Inhibitor on Patency of aAVF After PTA With PCB
Official title: Exploratory Research of PCSK9 Inhibitor on Patency of Autogenous Arteriovenous Fistula After Percutaneous Transluminal Angioplasty With Paclitaxel Releasing Balloon
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hemodialysis Access Failure
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2023-09-13
Enrollment: 40
Sex: ALL
Minimum age (years): 17
Maximum age (years): 76
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Autologous arteriovenous fistula (AVF) is the preferred vascular pathway type for maintenance hemodialysis (MHD) patients. The K/DOQI guidelines suggest that the use of percutaneous transluminal angioplasty (PTA) as the primary treatment for AVF stenosis is reasonable. However, the durability of PTA is limited. In order to reduce the risk of dysfunction recurrence after the intervention, there have been reports in recent years that drug-coated balloons (DCB) are used in the treatment of vascular stenosis in hemodialysis. Multiple factors have limited the efficacy of DCB. Previous studies on the related factors of hemodialysis access stenosis showed that Dyslipidemia was significantly related to the short initial patency rate, and Dyslipidemia was an important predictor of secondary patency loss. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new type of lipid-lowering drug that can prevent vascular calcification. Previous studies have shown that PCSK9 inhibitors have good lipid-lowering effects in both MHD patients and nondialysis patients, and the use of PSK9 inhibitors at the same dose as nondialysis patients is safe in MHD patients. There are currently few studies on the use of paclitaxel-releasing balloon dilation combined with PCSK9 inhibitors to improve autologous internal fistula. Therefore, the investigators applied a prospective, randomized, and controlled study method to preliminarily explore the effect of paclitaxel releasing balloon combined with PCSK9 inhibitor on improving the postoperative patency rate of AVF and the safety of the combined application.


Eligibility criteria: Inclusion Criteria:

1. Agree to join this study and sign an informed consent form
2. Age ≥ 18 years old and ≤ 75 years old, regardless of gender
3. Maintenance hemodialysis patients using autologous arteriovenous fistula (AVF), with a dialysis frequency of three times a week
4. AVF venous stenosis: The local stenosis rate exceeds 50% of the normal diameter of nearby blood vessels and is accompanied by at least one of the following conditions:

   1. The natural blood flow of the internal fistula is less than 500ml/min or has decreased by more than 25% compared to the previous examination result
   2. Unable to meet the required blood flow for dialysis prescription (blood flow\<200ml/min, and cannot be corrected after adjusting the puncture needle position)
   3. Decreased arterial pressure or increased venous pressure during dialysis (monitoring arterial pressure\<-120mmHg for more than 2 consecutive times or monitoring venous pressure\>120mmHg while maintaining 200ml/min blood flow)
   4. Difficulty in puncture: A qualified nurse who has difficulty puncturing for 3 consecutive days of hemodialysis (blood can only be drawn out after more than two punctures)
   5. Decreased dialysis adequacy \[arteriovenous fistula recirculation rate (RA)\>10%, or an increase of more than 25% compared to the previous examination result\] \[RA=(SA-A)/(SA-V) \* 100, dialysis to 1 hour: SA=blood flow adjusted to 20ml/min, ultrafiltration and dialysate flow stopped, after 2 minutes, artery Blood urea nitrogen concentration A=artery Blood urea nitrogen concentration V=vein Blood urea nitrogen concentration\]
   6. Abnormal signs of fistula.
5. Patients with primary Hypercholesterolemia \[LDL-C ≥ 130 mg/dl (≥ 3.4 mmol/L), and/or non-HDL-C≥ 160 mg/dl (≥ 4.1 mmol/L)\] or combine cardiovascular disease or assess patients with a high risk of cardiovascular disease

Exclusion Criteria:

1. MHD with AVG
2. Breastfeeding or Pregnant Women
3. Patients with central venous reflux obstruction
4. Patients with AVF feeding artery disease
5. Patients with severe Hypotension (systolic blood pressure\<90mmHg or diastolic blood pressure\<60mmHg, at least three times within one month before signing the informed consent)
6. Left ventricular Ejection fraction less than 30% or hemodynamic instability
7. Patients receiving immunotherapy or suspected/confirmed Vasculitis
8. Patients with coagulation dysfunction or a history of Thrombocytopenic purpura
9. Patients with vascular access infections or systemic active infections
10. Patients who are known to be allergic to PCSK9 inhibitors or paclitaxel
11. Patient's life expectancy is less than 12 months
12. Patients who are planning kidney transplantation or switching to Peritoneal dialysis
13. Patients participating in other intervention studies
14. The researcher judged that the subject's condition was not suitable for participation in this study

Primary outcomes:
measure: Value of vessel diameter
timeFrame: 24 week, 48 week
measure: Value of volume of blood flow
timeFrame: 24 week, 48 week
measure: Value of peak systolic velocity ratio（PSVR）
timeFrame: 24 week, 48 week
measure: Incidence of Re intervention of fistula
timeFrame: 48 week
Secondary outcomes:
measure: Endometrium
timeFrame: 24 week, 48 week
measure: RA
timeFrame: 24 week, 48 week
measure: BTM
timeFrame: 24 week, 48 week
measure: Adequacy of dialysis
timeFrame: 24 week, 48 week
measure: Blood routine
timeFrame: 12 week, 24 week, 48 week
measure: liver function
timeFrame: 12 week, 24 week, 48 week
measure: Concentration of blood sugar
timeFrame: 12 week, 24 week, 48 week
measure: Concentration of CRP
timeFrame: 12 week, 24 week, 48 week
measure: blood lipids
timeFrame: 12 week, 24 week, 48 week
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Yuanyuan Xie
state: Pudong
Study officials:
References: