Clinical trial NCT03860818: Improving Transplant Medication Safety Through A Technology and Pharmacist Intervention
Official title: Improving Transplant Medication Safety Through a Technology and Pharmacist (ISTEP) Intervention in Veterans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Transplant
Keywords: medication safety
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2019-03-04
Enrollment: 2196
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, cluster-randomized controlled clinical trial at 10 sites, randomizing 5 sites to standard clinical care and 5 to the intervention.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Medication safety issues in Veteran organ transplant recipients, including side effects and errors, are a major issue leading to graft failure and death. The causes of these events are complicated and involve fragmented care, communication breakdowns between the Veterans, providers and the different health care systems. This grant proposal seeks to improve medication safety within these high-risk Veterans, using two innovative components; the application of technology to leverage the massive amount of data contained within the electronic medical record in identifying Veterans with potential medication safety issues, coupled with a pharmacist-led intervention to improve the management and coordination of immunosuppression therapy. The completion of this prospective, multicenter, cluster randomized controlled clinical trial will provide evidence that these interventions can improve medication safety, clinical outcomes and costs and will be used to justify the dissemination of these interventions to all VAs caring for Veteran transplant recipients across the U.S.

Detailed description: Anticipated Impacts on Veterans Health Care: The first three essential strategies listed within the VA's Blueprint for Excellence encompass plans to improve care to vulnerable Veterans, deliver high quality care through achieving the "Triple Aim" and leverage the use of technology to improve the efficiency of care delivery. The intervention this grant proposes focuses on improving medication safety and care coordination within a high risk vulnerable Veteran population, leverages the use of informatics and analytics to support this intervention, and aims to demonstrate improved care at reduced costs through the pharmacist intervention; thus, perfectly aligning with these three essential components of the Blueprint. The overarching goal of this study is to develop a feasibly deployable, technology-enabled intervention that will demonstrate substantial improvements in immunosuppressant medication safety, clinical outcomes and health care costs in Veteran organ transplant recipients; demonstrating this through a randomized controlled trial will provide sufficient evidence to further develop a VA-specific pharmacist learning collaborative aimed at improving care and reducing costs for Veteran organ transplant recipients across the entire VA system.

Background: Organ transplant is the gold-standard treatment for patients with end organ diseases of the kidney, liver, heart and lungs, as it substantially improves survival and quality of life. Over the past 20 years, the use of contemporary immunosuppression has reduced the risk of acute rejection rates by upwards of 80%; yet long-term allograft survival remains suboptimal. Studies have demonstrated that causes of late graft loss is predominantly driven by immunosuppression adverse events and late allograft rejection episodes from medication errors and non-adherence, which encompass issues directly related to medication safety. The investigators' research demonstrates that medication errors occur in nearly two-thirds of transplant recipients, leading to hospitalization in 1 in 8 recipients. Recipients that develop significant medication errors are at considerably higher risk of graft loss, leading to higher costs and mortality. Thus, in order to improve medication safety and long-term outcomes in transplant recipients, enhancements in immunosuppressant therapy management is needed.

Objectives: The central hypothesis for the ISTEP study (Improving Transplant Medication Safety through a TEchnology and Pharmacist Intervention) is that pharmacist-led immunosuppressant therapy management, facilitated through the use of innovative technology, will significantly improve immunosuppressant safety and clinical outcomes in Veteran transplant recipients.

Methods: This is a 24-month, prospective, cluster-randomized controlled clinical trial at 10 sites, randomizing 5 sites to standard clinical care and 5 to standard care and the technology-enabled pharmacist intervention. The technology component of this intervention consists of the use of an expanded dashboard system that has already demonstrated effectiveness in improving immunosuppression monitoring. The dashboard performs population-level surveillance of transplant recipients and identifies those with potential drug-related problems, including non-adherence, drug interactions, missing and worrisome trends in labs; then providing a real-time alert to the pharmacist, who will determine its relevance and intervene in an appropriate protocol-guided manner. Effectiveness will be determined by comparing the rates of hospitalizations and ER visits between groups, while adjusting for baseline patient, provider and facility characteristics. Secondary measures include comparing healthcare costs and determining dashboard functionality, dashboard actionability and pharmacist intervention types and acceptance rates. The investigators will also assess the overall incidence and severity of drug-related problems and graft and patient survival rates and compare these between the intervention and control sites.

Eligibility criteria: Inclusion Criteria:

* Veteran organ transplant recipients will be identified using International Classification of Diseases (ICD) 9/10 codes from the VA electronic health record (CPRS).
* Patients must have an active code stating they are a recipient of an organ transplant.
* The following codes will be utilized - ICD-9 codes:

  * V42.0
  * V42.1
  * V42.6
  * V42.7
  * V42.83
  * V42.84
  * 996.81
  * 996.82
  * 996.83
  * 996.84
  * 996.86
  * 52.80

OR

* oICD-10 codes:

  * C80.2
  * T86.1
  * T86.10
  * T86.11
  * T86.12
  * T86.13
  * T86.19
  * T86.2
  * T86.20
  * T86.21
  * T86.22
  * T86.23
  * T86.290
  * T86.298
  * T86.3
  * T86.30
  * T86.31
  * T86.32
  * T86.33
  * T86.39
  * T86.4
  * T86.40
  * T86.41
  * T86.42
  * T86.43
  * T86.49
  * T86.810
  * T86.811
  * T86.812
  * T86.818
  * T86.819
  * T86.9
  * Z48.2
  * Z48.21
  * Z48.22
  * Z48.23
  * Z48.24
  * Z48.280
  * Z48.288
  * Z48.298
  * Z94.0
  * Z94.1
  * Z94.2
  * Z94.3
  * Z94.4
  * Z94.83

AND

* Actively receiving at least one anti-rejection medication dispensed by the VA site.
* These medications include:

  * tacrolimus
  * cyclosporine
  * azathioprine
  * mycophenolate
  * sirolimus
  * everolimus
  * belatacept

Exclusion Criteria:

* There are no exclusion criteria for patients in this study as recruitment is at the level of the VA site.
* All veterans meeting inclusion criteria will be monitored by the dashboard system and will be included in the outcomes assessment.
* Patients may enter or exit the study in a rolling manner, which will be accounted for during analyses.

Primary outcomes:
measure: Any Hospitalization or Any Emergency Room Visits
timeFrame: 24-months
Secondary outcomes:
measure: Total Estimated Health Care Costs, Compared Between the Intervention and Control Groups
timeFrame: 27-months
measure: Number of Participants With Graft Survival
timeFrame: 27-months
measure: Patient Survival- Percentage of Patients That Died During Study
timeFrame: 27-months
measure: Medication Safety Issues
timeFrame: 23-months
measure: Clinically Relevant Alerts
timeFrame: 22-months
measure: Dashboard-Accepted Interventions
timeFrame: 23-months
measure: Average Time Responding to Dashboard Alerts
timeFrame: 23-months
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
Study officials:
affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC
name: David J. Taber, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taber DJ, Ward R, Axon RN, Walker RJ, Egede LE, Gebregziabher M. The Impact of Dual Health Care System Use for Obtaining Prescription Medications on Nonadherence in Veterans With Type 2 Diabetes. Ann Pharmacother. 2019 Jul;53(7):675-682. doi: 10.1177/1060028019828681. Epub 2019 Feb 6.
citation: Taber DJ, Ward RC, Buchanan CH, Axon RN, Milfred-LaForest S, Rife K, Felkner R, Cooney D, Super N, McClelland S, McKenna D, Santa E, Gebregziabher M. Results of a multicenter cluster-randomized controlled clinical trial testing the effectiveness of a bioinformatics-enabled pharmacist intervention in transplant recipients. Am J Transplant. 2023 Dec;23(12):1939-1948. doi: 10.1016/j.ajt.2023.08.004. Epub 2023 Aug 9.
citation: Hall CL, Fominaya CE, Gebregziabher M, Milfred-LaForest SK, Rife KM, Taber DJ. Improving Transplant Medication Safety Through a Technology and Pharmacist Intervention (ISTEP): Protocol for a Cluster Randomized Controlled Trial. JMIR Res Protoc. 2019 Oct 1;8(10):e13821. doi: 10.2196/13821.