Real-World Safety Analysis of Paclitaxel Devices Used for the Treatment of Peripheral Arterial Disease

Peripheral Arterial Disease Clinical Trial

Official title:

Real-World Safety Analysis of Paclitaxel Devices Used for the Treatment of Peripheral Arterial Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04647643
• Other study ID #: 20203069FH
• Secondary ID: 6292-2020-2AS-10
• Status: Completed
• Start date: November 20, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2022
• Source: Lahey Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Treatment with paclitaxel-based endovascular devices (PED) has become a common treatment option for patients with peripheral artery disease (PAD) involving the femoral-popliteal artery. However, an aggregate level meta-analysis identified an association between the use of PED and increased all-cause mortality at both two and five-year follow-up intervals, though there are significant limitations of these analyses. Exploration of real-world data has been suggested as a means to further investigate the safety of PED. The current study explores the association of PED and mortality in real-world data using U.S. commercial claims from the FAIR Health data warehouse.

Description:

Treatment with paclitaxel-based endovascular devices (PED) has become a common treatment option for patients with peripheral artery disease (PAD) involving the femoral-popliteal artery. However, an aggregate level meta-analysis identified an association between the use of PED and increased all-cause mortality at both two and five-year follow-up intervals, though there are significant limitations of these analyses. Exploration of real-world data has been suggested as a means to further investigate the safety of PED. The current study explores the association of PED and mortality in real-world data using U.S. commercial claims from the FAIR Health data warehouse. This study aims to evaluate the relative safety of paclitaxel used as an antiproliferative agent in the treatment of symptomatic PAD in a real-world scenario. We will analyze Paclitaxel Drug-Coated Balloons (DCB) and Paclitaxel Drug-Eluting Stents (DES), in aggregate and as unique exposures using propensity score-matched survival analysis. (Inverse probability of Treatment Weighting). Commercial claims of patients who underwent endovascular interventional treatment of the femoral or popliteal arteries for symptomatic PAD between 1/1/15 and 12/31/2019 will form the study population. Three separate safety analyses will be performed. 1. Paclitaxel Drug coated balloons (DCB) as compared with propensity-matched patients treated with plain transluminal balloon angioplasty (PTA). 2. Paclitaxel delivering Drug-Eluting Stents (DES) as compared with propensity-matched cases using bare-metal stents (BMS). 3. Patients treated with either paclitaxel DCB or paclitaxel DES (any PTX) compared with propensity-matched controls (non-PTX,with DCB patients, matched to patients treated with PTA, and DES patients matched to patients treated with BMS). All proposed analyses will be performed using R 4.01 implemented within the DELTA analytic engine. DELTA is an active surveillance safety system that can monitor clinical data repositories for safety signals and has been validated to support risk-adjusted prospective safety surveillance analyses of complex clinical datasets.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8000
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients, age 18 or older, who had a health insurance claim for outpatient endovascular treatment of the femoral or popliteal arteries for symptomatic PAD will be included. The diagnosis and treatment of PAD in the femoral and popliteal arteries will be identified by CPT/HCPCS and ICD-9 and ICD-10 PCS codes.
• Presence of at least one additional outpatient or inpatient claims, at least 12 months following the index procedure, in order to demonstrate continued enrollment in health insurance coverage.

Exclusion Criteria:

• Age <18 years
• No qualifying peripheral arterial endovascular procedure
• Inpatient procedure
• Patients without any linked claim record more than 12 months after the index procedure, not known to have died or entered hospice care within the first 12 months

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Paclitaxel
Paclitaxel to treat peripheral arterial disease

Locations

Country	Name	City	State
United States	Lahey Clinic, Inc	Burlington	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Lahey Clinic	National Evaluation System for health Technology Coordinating Center (NESTcc), Society for Vascular Surgery Patient Safety Organization

Country where clinical trial is conducted

United States, 

References & Publications (13)

Austin PC. Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat. 2011 Mar-Apr;10(2):150-61. doi: 10.1002/pst.433. — View Citation

Behrendt CA, Sedrakyan A, Peters F, Kreutzburg T, Schermerhorn M, Bertges DJ, Larena-Avellaneda A, L'Hoest H, Kölbel T, Debus ES. Editor's Choice - Long Term Survival after Femoropopliteal Artery Revascularisation with Paclitaxel Coated Devices: A Propens — View Citation

Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, Snyder SA, O'Leary EE, Tepe G, Scheinert D, Zeller T; Zilver PTX Investigators. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the — View Citation

Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, Zeller T, Roubin GS, Burket MW, Khatib Y, Snyder SA, Ragheb AO, White JK, Machan LS; Zilver PTX Investigators. Paclitaxel-eluting stents show superiority to balloon angioplasty and bare metal stents — View Citation

Hsieh FY, Lavori PW, Cohen HJ, Feussner JR. An overview of variance inflation factors for sample-size calculation. Eval Health Prof. 2003 Sep;26(3):239-57. Review. — View Citation

Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. — View Citation

Kumar A, Matheny ME, Ho KK, Yeh RW, Piemonte TC, Waldman H, Shah PB, Cope R, Normand SL, Donnelly S, Robbins S, Resnic FS. The data extraction and longitudinal trend analysis network study of distributed automated postmarket cardiovascular device safety s — View Citation

Resnic FS, Gross TP, Marinac-Dabic D, Loyo-Berrios N, Donnelly S, Normand SL, Matheny ME. Automated surveillance to detect postprocedure safety signals of approved cardiovascular devices. JAMA. 2010 Nov 10;304(18):2019-27. doi: 10.1001/jama.2010.1633. — View Citation

Resnic FS, Majithia A. Registry-Based Surveillance of Medical-Device Safety. N Engl J Med. 2017 May 18;376(20):1995. doi: 10.1056/NEJMc1704006. — View Citation

Rocha-Singh KJ, Duval S, Jaff MR, Schneider PA, Ansel GM, Lyden SP, Mullin CM, Ioannidis JPA, Misra S, Tzafriri AR, Edelman ER, Granada JF, White CJ, Beckman JA; VIVA Physicians, Inc. Mortality and Paclitaxel-Coated Devices: An Individual Patient Data Met — View Citation

Secemsky EA, Kundi H, Weinberg I, Jaff MR, Krawisz A, Parikh SA, Beckman JA, Mustapha J, Rosenfield K, Yeh RW. Association of Survival With Femoropopliteal Artery Revascularization With Drug-Coated Devices. JAMA Cardiol. 2019 Apr 1;4(4):332-340. doi: 10.1 — View Citation

Secemsky EA, Kundi H, Weinberg I, Schermerhorn M, Beckman JA, Parikh SA, Jaff MR, Mustapha J, Rosenfield K, Yeh RW. Drug-Eluting Stent Implantation and Long-Term Survival Following Peripheral Artery Revascularization. J Am Coll Cardiol. 2019 May 28;73(20) — View Citation

Vidi VD, Matheny ME, Resnic FS. Post-marketing device safety surveillance. Contemp Clin Trials. 2011 May;32(3):307-8. doi: 10.1016/j.cct.2011.02.002. Epub 2011 Feb 28. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Survival for age groups	Freedom from death in the age groups 18-34, 35-44, 45-54, 55-64, 65-74, 75 and above	4 years and 2 years post intervention
Other	Survival for demographics and special baseline variables	Freedom from death in females, patients with claudication, CKD and dialysis, history of CAD, history of cancer	4 years and 2 years post intervention
Other	Survival for special treatment category	Freedom from death in patients with patients receiving paclitaxel-coated device as a second procedure	4 years and 2 years post intervention
Primary	Survival	Freedom from death of any cause	4 years post intervention
Secondary	Survival	Freedom from death of any cause	2 years post intervention
Secondary	Retreatment	Retreatment with repeat revascularization (open or endovascular)	2 years post intervention
Secondary	Amputation	Freedom from amputation	2 years post intervention

External Links

•   McKeown L. Two trials halted in wake of study linking paclitaxel-coated devices to deaths in PAD
•   Society of Vascular Surgery Vascular Quality Initiative.
•   U.S. Food and Drug Administration (FDA). FDA Executive Summary: Circulatory System Devices Panel Meeting