A Prospective Trial to Assess Cost and Clinical Outcomes of a Clinical Pharmacogenomic Program

NCT02297126 | Completed

• 2 other identifiers: 1401206188U01HG007762-01
• Study Type: interventional
• Target: 4,465
• Locations: 1 country
• Sites: 1

Brief Summary

The INGenious trial will prospectively enroll a total of 6,000 patients, with 2,000 patients assigned to a pharmacogenetic testing arm and 4,000 to a control arm who will be followed, but not tested. It is randomized between an intervention arm and one that receives no intervention in order that the genotyped group can be compared with one in which undisturbed, routine clinical care is carried out in patients taking the same drugs. Both arms will be followed for a year after being prescribed a targeted medication. Patients randomized into the intervention arm that are prescribed one or more of the 24 targeted index medication will receive pharmacogenomic testing using a custom micro-array measuring 51 Single nucleotide polymorphisms in 16 genes. The study is being conducted by the Indiana University School of Medicine and the Indiana University Institute of Personalized Medicine in collaboration with the Eskenazi and Indiana University Health Systems and will evaluate the economic and clinical outcomes associated with embedding a pharmacogenomics program in a system that serves as the primary health care safety-net in Indianapolis, Indiana. By successfully implementing a pharmacogenomics program and integrating it with the Electronic Health Record and Clinical Decision Support system, physicians will be able to optimize patient care by delivering tailored therapeutic decisions based on the patient's individual genetics.

Conditions

Adverse Drug Reaction

Outcome Measures

Primary Outcomes (1)

• Financial impact on the total cost of patient care resulting from implementation of a Pharmacogenetics testing program within a safety-net and Academic healthcare system

  Analysis of cost of care (measured in U.S. dollars) data from the Eskenazi and Indiana University Health electronic medical records and billing systems for patients in the study. Charge data collected from monthly Eskenazi and IU Health System reports generated for the state hospital association. Categories of inpatient and outpatient charges include costs for medications, facility, laboratory, treatment, professional, and other sources. Data will be collected for each patient in the control and intervention arm beginning the day that the treating physician prescribes one or more targeted medication and will continue to be collected for 12 calendar months. Study enrollment period 2.5 years

  Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed

Secondary Outcomes (2)

• Impact of implementing a Pharmacogenetics program on Clinical Outcomes (incidence and severity of adverse events, frequency of healthcare visits, length of hospital stay, and readmissions) within a safety-net and Academic healthcare system

  Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed

• Impact of implementing a Pharmacogenetics program on prescribing patterns within a safety-net healthcare system

  Study enrollment period of 2.5 years with individual patient data collection period of 12 month after one of more targeted medication is prescribed

Study Arms (2)

Control Arm

NO INTERVENTION

4,000 patients receiving a new prescription for targeted medication(s) randomized into the control arm receive standard care (no intervention affecting drug selection, dosage, dosage form, frequency and duration of therapy). Healthcare costs and adverse events data collected and analyzed for 12 months from time of entry into study. List of targeted medications: codeine, amitriptyline, aripiprazole, atazanavir, atomoxetine, azathioprine, citalopram, clopidogrel, cyclophosphamide, doxepin, efavirenz, escitalopram, esomeprazole, fluconazole, simvastatin, fluorouracil, phenytoin, quetiapine, glyburide, lansoprazole, mercaptopurine, methadone, methotrexate, nortriptyline, omeprazole, pantoprazole, rasburicase, tacrolimus, thioguanine, tramadol, venlafaxine, voriconazole and warfarin

Pharmacogenetic Intervention Arm

EXPERIMENTAL

2,000 patients receiving new prescription for targeted medication(s) identified in the control arm will be randomized to the intervention arm, consented and a tests will be performed from a blood sample. The treating physicians will be provided with the pharmacogenetic information and will determine if intervention is appropriate. Physician may elect to stay the course of therapy or alter drug selection, dosage, dosage form, frequency or duration of therapy based on the pharmacogenetic test results and input from clinical pharmacology consultations (if requested). Patients in the intervention arm will have their overall healthcare costs and clinical outcomes (specifically adverse events) followed and analyzed for a 1 year period from the time that they are entered into the study

Other: Pharmacogenetic Intervention Arm (pharmacogenetic testing)

Interventions

Pharmacogenetic Intervention Arm (pharmacogenetic testing) OTHER

In the design of this trial, pharmacogenetic testing will be triggered by the incident prescription of one or more of the targeted medications listed in the control arm. The pharmacogenetic array to be used incorporates 51 genetic variants for the following 16 genes/transporters: ATP-binding cassette sub-family C member 2, ATP-binding cassette, sub-family C, member 4, Cytochrome P450 2B6, Cytochrome P450 2C19, Cytochrome P450 2C9, Cytochrome P450 2D6, Cytochrome P450 3A4/3A5, Cytochrome P450 4F2, Dihydropyrimidine dehydrogenase, Glucose-6-Phosphate Dehydrogenase, Human Leukocyte antigen-B, I interleukin-28B, Inosine Triphosphatase, Solute Carrier Organic Anion Transporter Family, Member 1B, Thiopurine methyltransferase and V vitamin K epoxide reductase complex, subunit 1.

Pharmacogenetic Intervention Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing consent to participation in the trial;
• Adults aged 18 and over;
• Receiving care at Eskenazi Health or Indiana University Health Systems for 1 year or more;
• Prescribed an index medication.
• No documented prescription of the index medication for the past year.
• The study limit of enrollment (500) for that medication has not been reached
• A single tube of whole blood can be obtained, and
• Able to follow study procedures. -

You may not qualify if:

• No subject will be excluded from the study on the basis of ethnicity or race. We will include all minorities.
• Patients will be excluded if they:
• Cannot or do not consent to participate;
• are unable to provide 5cc of whole blood, or it cannot be obtained;
• if they are an employee or student under the supervision of any of the investigators.

Sponsors & Collaborators

• Indiana University: lead
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (1)

Eskenazi Health System

Indianapolis, Indiana, 46250, United States

Location

Related Publications (2)

• Levy KD, Decker BS, Carpenter JS, Flockhart DA, Dexter PR, Desta Z, Skaar TC. Prerequisites to implementing a pharmacogenomics program in a large health-care system. Clin Pharmacol Ther. 2014 Sep;96(3):307-9. doi: 10.1038/clpt.2014.101. Epub 2014 May 7.

  PMID: 24807457 BACKGROUND

• Fulton CR, Zang Y, Desta Z, Rosenman MB, Holmes AM, Decker BS, Zhang Y, T Callaghan J, Pratt VM, Levy KD, Gufford BT, Dexter PR, Skaar TC, Eadon MT. Drug-gene and drug-drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial. Pharmacogenomics. 2019 Apr;20(6):397-408. doi: 10.2217/pgs-2018-0205. Epub 2019 Feb 20.

  PMID: 30784356 DERIVED

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Paul R Dexter, MD

  Indiana University School of Medicine, Regenstrief Institute, Eskenazi Health

  PRINCIPAL INVESTIGATOR

• Todd Skaar, PhD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 5, 2014
• First Posted: November 21, 2014
• Study Start: March 1, 2015
• Primary Completion: May 3, 2019
• Study Completion: May 3, 2019
• Last Updated: January 8, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)