Developing a health system-wide alteplase dosing protocol for catheter clearance

Milovac BM, Skledar SJ, Campbell RJ University of Pittsburgh Medical Center and University of Pittsburgh School of Pharmacy

Pittsburgh, PA 15213

BACKGROUND

q Conducted a retrospective review of purchase data for the 2 mg/2 mL vial for calendar year (CY) 2012 [Figure 1]

q Calculated the projected costs of compounding 1 mg and 2 mg syringes §  Determined annual cost savings for

each dose [Figures 1 and 2] q Performed a comprehensive review of

the literature to evaluate safety and efficacy of 1 mg and 2 mg dosing regimens [Tables 1 and 2]

q Completed a benchmarking survey of academic and community hospital practices related to tPA for catheter clearance

q Collaborated with an interdisciplinary expert team to develop guidelines for eventual System Pharmacy and Therapeutics Committee (SPTC) approval

q Planned for a three-month pilot across four facilities to evaluate outcome, process, and economic impact

METHODS

RESULTS

CONCLUSION

OBJECTIVE

Disclosure: Authors of this presentation have nothing to disclose concerning possible financial or personal relationships with commercial entities.

References: Fink et al. Ann Pharmacother 2004;38(2):351-2. Davis et al. Am J Health Syst Pharm 2000;57(11):1039-45. Sapienza et al. Hosp Pharm 2015 Apr (in press). Haymond et al. J Vasc Access 2005;6(2):76-82.

q The purpose of this project was to create an evidence-based, cost-effective tPA dosing protocol for a health system

q Recombinant alteplase is a tissue plasminogen activator (tPA) §  Binds fibrin §  Converts plasminogen to plasmin §  Produces fibrinolysis

q Commercially available in 2 mg/2 mL (Cathflo Activase®) vial §  Approved for restoration of function to

central venous catheter (CVC) access devices

q Additional indications for tPA §  Acute myocardial infarction §  Acute, ischemic cerebrovascular

accident §  Pulmonary embolism

q Cathflo Activase® national shortage in 2012-13 prompted hospitals and dialysis centers to evaluate different mixing and dosing strategies §  Facilities could experience significant

cost savings by using 100 mg tPA bulk vials to batch-prepare 1 mg syringes

§  Question for UPMC: Does the 1 mg dose show equivalent safety and efficacy to the 2 mg dose?

UPMC Annual Spend: $2,425,759.44*

22,728 vials purchased (2 mg vial)

Cost savings: $1,003,652.57 (100% conversion)

UPMC spend estimate: $1,422,106.87

228 vials required (100 mg vial = 100 x 1 mg dose)

Fink, 2004 (1B) Davis, 2000 (1C) Sapienza, 2014 (1C)

Design Unblinded, randomized trial Open-label dose escalation Comparative observational study

Setting Cleveland Clinic University of Wisconsin Hospitals and Clinics

HealthEast Bethesda Hospital; St. Paul, MN

n 45 patients 61 lumens

(CVC)

58 patients 66 lumens

(Midline, CVC)

168 patients Peripherally inserted

central catheters (PICC)

Treatment 1 mg: 37 2 mg: 24

Escalating dose: 0.5 mg, 1 mg, 2 mg (60-min dwell time)

1 mg or 2 mg, once or twice

Success rate (SR)

[cleared catheter]

1 mg once (81.1%) or twice (85.5%)

2 mg once (83.3%) or twice (87.5%)

0.5 mg: 86.2%

1 mg: 94.8%

2 mg: 96.5%

1 mg once (85.6%) or twice (93.3%)

2 mg once (87.2%) or twice (94.4%)

Additional findings

No difference in one dose (RR 0.95, 95% CI 0.69 to 1.29) vs. two doses (RR 0.94, 95% CI 0.71 to 1.24). P = NS.

Four patients did not meet all study criteria. Removing them, 0.5 mg tPA SR = 92.6%.

No statistical difference between 1 mg and 2 mg groups. P = NS.

q Projected Savings: §  Assuming 100% conversion to 1 mg dose, annual savings exceeds $1 million

§  75% conversion savings estimates amount to $752,739.43 §  Allows for potential outpatient dialysis center exclusion (storage convenience)

q Literature Summary: §  Three studies each in non-hemodialysis and dialysis patients showed no significant

differences between doses §  One retrospective analysis of dialysis patients showed a statistically significant

improvement in clearance for 2 mg q  Benchmarking Survey:

§  17 surveyed sites have successfully implemented the 1 mg dosing strategy

Figure 1. CY 2012 Purchases of 2 mg/2 mL Vials Figure 2. Savings Projections Using 100 mg Vials to Compound 1 mg Syringes

Haymond, 2005 (1C) Nguyen, 2004 (1C) Meers, 1999 (1C) Yaseen, 2013 (1C)*

Design Prospective observational study Retrospective analysis Retrospective analysis Retrospective analysis

Setting Vancouver General Hospital (tertiary care) Holy Name Hospital (NJ) Kingston General Hospital

(CAN) Hotel-Dieu Grace Hospital

(CAN)

n 50 patients 52 occlusion episodes 17 patients 21 catheters 40 instances

237 patients

Treatment 1 mg,

1 or 2 doses (60-min dwell time)

1.5 mg (30-min dwell time) 1 mg

1 mg: n = 129 2 mg: n = 108

(30-min dwell time)

SR 1 dose: 72% 2 doses: 83%

Patients split into 3 groups with specific criteria.

Groups had SR’s of 84%, 97% and 100%.

97.5%

1 mg: 80.6% 2 mg: 89.8%

p = 0.05

Table 1. Evidence for Non-hemodialysis Patients

Table 2. Evidence for Hemodialysis Patients

*Mean catheter survival time was 782 d (1 mg) vs. 955 d (2mg); p = 0.019. Neither group reached 50% catheter removal rate by the end of the follow-up period (median catheter survival time could not be calculated). HR for catheter removal in 1 mg group was 2.75 (95% CI = 1.25-6.04).

q 1 mg and 2 mg doses show equivalent safety and efficacy in the literature for non-hemodialysis catheter clearance §  Majority of hemodialysis catheter studies also demonstrate equivalence

q Conversion to a 1 mg dose will have a positive economic impact q Observation of current national practice supports this strategy q Post-pilot data will be assessed to determine successful implementation §  Need for repeat dosing following a 60-minute dwell time will mark clearance success

*Spend if 100 mg bulk vial used to make 22,728 of 2 mg doses: $2,846,935 [50 doses per vial x 455 vials needed]

Nguyen et al. Am J Health Syst Pharm 2004;61(18):1922-4. Meers et al. CANNT J 1999;9(4):25-8. Yaseen et al. Hemodial Int 2013;17(3):434-40.