Pharmacogenetic Testing Among Home Health Patients

Study Overview
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Brief Summary
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Patients meeting eligibility criteria will be randomized into two groups, one receiving pharmacogenetic testing and the other not receiving pharmacogenetic testing. In this open-label trial, a pharmacist will make medication therapy recommendations using YouScript® Personalized Prescribing System for patients who receive genetic testing and standard drug information resources per usual for patients who do not undergo pharmacogenetic testing.

Detailed Description
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Both groups will be followed for 60 days. The number of re-hospitalizations and emergency department (ED) visits will be recorded as well as time to first re-hospitalization and time to first ED visit. Select Outcome and Assessment Information Set (OASIS) metrics (e.g. M1034, M1242, M1710, M1720, M1745, M2110) and Patient Health Questionnaire (PHQ)-2 will be evaluated and documented at time of admission to home health, at 30 days, and at 60 days for improvement in overall status, pain, confusion, anxiety, depression, disruptive behavior, and the need for assistance with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). The number of falls will be collected as well as the proportion of YouScript® recommendations accepted by study pharmacist and passed on to clinicians and the proportion of recommendations accepted by clinicians.

Official Title
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A Pilot Prospective, Randomized Controlled Trial Assessing the Clinical Impact of Integrated Pharmacogenetic Testing on Selected OASIS Metrics, Re-hospitalizations and Emergency Department Visits

Conditions
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Adverse Drug Events, Adverse Drug Reactions, Drug Interaction Potentiation, Drug Metabolism, Poor, CYP2D6-RELATED, Drug Metabolism, Poor, CYP2C19-RELATED, Cytochrome P450 Enzyme Deficiency, Cytochrome P450 CYP2D6 Enzyme Deficiency, Cytochrome P450 CYP2C9 Enzyme Deficiency, Cytochrome P450 CYP2C19 Enzyme Deficiency, Cytochrome P450 CYP3A Enzyme Deficiency, Poor Metabolizer Due to Cytochrome P450 CYP2C9 Variant, Poor Metabolizer Due to Cytochrome p450 CYP2C19 Variant, Poor Metabolizer Due to Cytochrome P450 CYP2D6 Variant

Intervention / Treatment
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* Genetic: Pharmacogenetic testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 or older. Willing and able to provide informed consent for study participation either directly or by a legally authorized representative (LAR). Presently taking or beginning treatment with at least one of the following oral forms of medication (excluding medications taken PRN) (generic name given with major U.S. brand name given in parentheses). These medications are subject to significant drug-gene interactions as defined by FDA boxed warning, FDA cautionary labeling, clinical literature or a YouScript® algorithm-predicted significant effect: Amitriptyline (Elavil), Aripiprazole (Abilify), Atomoxetine (Strattera), Carvedilol (Coreg), Celecoxib (Celebrex), Citalopram (Celexa), Clobazam (Onfi), Clomipramine (Anafranil), Clopidogrel (Plavix), Clozapine (Clozaril), Codeine [Tylenol #3 (combo)], Desipramine (Norpramin), Dextromethorphan (Delsym), Diazepam (Valium), Doxepin (Sinequan), Escitalopram (Lexapro), Esomeprazole (Nexium), Fesoterodine (Toviaz), Flecainide (Tambocor), Fluoxetine (Prozac), Flurbiprofen (Ansaid), Fluvoxamine (Luvox), Haloperidol (Haldol), Hydrocodone , Ibuprofen (Motrin), Iloperidone (Fanapt), Imipramine (Tofranil), Indomethacin (Indocin), Meloxicam (Mobic), Metoprolol (Toprol XL), Mexiletine (Mexitil), Nortriptyline (Pamelor), Omeprazole (Prilosec), Oxycodone (Oxycontin), Paroxetine (Paxil), Perphenazine (Trilafon), Phenobarbital (Luminal), Phenytoin (Dilantin), Pimozide (Orap), Piroxicam (Feldene), Proguanil [(Malarone (combo)], Propafenone (Rythmol), Propranolol (Inderal), Risperidone (Risperdal), Sertraline (Zoloft), Tetrabenazine (Xenazine), Thioridazine (Mellaril), Timolol (Apotimol), Tolterodine (Detrol), Torsemide (Demadex), Tramadol (Ultram), Trimipramine (Surmontil), Venlafaxine (Effexor), Voriconazole (Vfend), Vortioxetine (Brintellix), Warfarin (Coumadin). Exclusion Criteria: Previous CYP testing (CPT codes 81225, 81226, 81227, 81355, 81401) History of organ transplant (199.2; 238.77; 414.06; 414.07; 996.80-996.89; E878.0; V42.0-V42.7; V42.81-V42.84; V42.89; V42.9; V45.87; V49.83; V58.44) Current malabsorption syndrome (579.0), including the following: Intestinal malabsorption (579.8, 579.9), Postoperative malabsorption (579.3), or Short bowel syndrome (579.3) Treatment of invasive solid tumors or hematologic malignancies in the last year, excluding in situ cancers or non-melanoma skin cancer (basal cell carcinoma) End Stage Renal Disease (ESRD) Persistent acute renal failure: complete loss of kidney function >4 weeks (requiring dialysis) Renal failure by: Glomerular filtration rater (GFR): SCr > 3 times baseline or GFR decreased 75% or SCr ≥4 mg/dL; acute rise ≥0.5 mg/dL; OR Urine Output (UO): UO < 0.3 mL/kg/h 24 h (oliguria) or anuria 12 h.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Controls (not tested)<br>Treatment as usual (e.g. review of potential drug-drug interactions via Lexicomp Online) | |
| Active Comparator: Intervention (tested)<br>Patients in the tested group will receive pharmacogenetic testing via YouScript® Personalized Prescribing System. The study pharmacist will review drug-drug interactions (DDI), drug-gene interactions (DGI), and drug-drug-gene interactions (DDGI) using YouScript® to provide drug therapy recommendations to prescribers. | Genetic: Pharmacogenetic testing<br>* Pharmacogenetic testing via YouScript® Personalized Prescribing System<br>* Other names: YouScript® Personalized Prescribing System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Re-hospitalizations at 30 and 60 Days | The primary outcomes included the number of re-hospitalizations at 30 and 60 days. | 30 days, 60 days post discharge | 
| The Primary Outcomes Included the Number of Emergency Department Visits at 30 and 60 Days. | Assessed the number of Emergency Department visits at 30 and 60 days post discharge with pharmacogenetic testing and YouScript® Personalized Prescribing system. | 30 days, 60 days post discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to 1st Re-hospitalization | To assess time to first re-hospitalization, we compared the exploratory time-to-event outcomes between the tested and untested groups at 30 days and 60 days. These outcomes were measured using cumulative percentage events at 30 and 60 days, referring to the percentage of subjects re-hospitalized before or at 30 and 60 days. | 30 days, 60 days | 
| Time to 1st Emergency Department Visit | To assess time to first emergency department visit, we compared the exploratory time-to-event outcomes (time to 1st ED visit) between the tested and untested groups at 30 days and 60 days. These outcomes were measured using cumulative percentage events at 30 and 60 days, referring to the percentage of subjects who visited the emergency department before or at 30 and 60 days. | 30 days, 60 days | 
| Overall Status as Measured by Outcome and Assessment Information Set (OASIS) Scale | We assessed the impact of genetic testing on overall status according to OASIS M1034 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M1034, one data point in the OASIS system, measures overall patient status on a scale of 0 to 3, with a lower score indicating better overall status. | 30 days, 60 days post discharge | 
| Pain as Measured by OASIS Scale | We assessed the impact of genetic testing on patient pain frequency according to OASIS M1242 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M1242, one data point in the OASIS system, measures patient pain frequency on a scale of 0 to 4, with a lower score indicating less frequent pain. | 30 days, 60 days post discharge | 
| Confusion as Measured by OASIS Scale | We assessed the impact of genetic testing on frequency of confusion according to OASIS M1710 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M1710, one data point in the OASIS system, measures patient confusion frequency on a scale of 0 to 4, with a lower score indicating less frequent confusion. | 30 days, 60 days post discharge | 
| Anxiety as Measured by OASIS Scale | We assessed the impact of genetic testing on frequency of anxiety according to OASIS M1720 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M1720, one data point in the OASIS system, measures patient confusion frequency on a scale of 0 to 3, with a lower score indicating less frequent confusion. | 30 days, 60 days post discharge | 
| Depression as Measured by Patient Health Questionnaire (PHQ)-2 Scale | We assessed the impact of genetic testing on frequency of depressive mood according to PHQ-2 at 30 and 60 days post discharge. PHQ-2 evaluates patient depression by assessing two factors: frequency of little interest or pleasure in doing things and frequency of feeling down, depressed, or hopeless. This outcome measure assessed the second factor, frequency of feeling down or depressed. The scale for this factor ranges from 0 to 3, with a lower score represented less frequent depressive feelings. | 30 days, 60 days post discharge | 
| Disruptive Behavior as Measured by OASIS Scale | We assessed the impact of genetic testing on frequency of disruptive behavior according to OASIS M1745 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M1745, one data point in the OASIS system, measures frequency of disruptive behavior by patient on a scale of 0 to 5, with a lower score indicating less frequent disruptive behavior. | 30 days, 60 days post discharge | 
| Activities of Daily Living as Measured by OASIS Scale | We assessed the impact of genetic testing on the frequency of activities of daily living (ADL) and instrumental activities of daily living (IADL) assistance according to OASIS M2110 at 30 and 60 days post discharge. OASIS measures various data items to assess home health care quality and performance. OASIS M2110, one data point in the OASIS system, measures frequency of receiving ADL/IADL assistance on a scale of 0 to 5, with a lower score indicating less frequent assistance. | 30 days, 60 days post discharge | 
| Number of Falls as Measured by Tabulation | To assess whether YouScript® testing decreases falls | 60 days | 
| Number of Pharmacist-accepted of Recommendations as Measured by Tabulation | To assess the proportion of YouScript® Personalized Prescribing System recommendations accepted by the study pharmacist and passed on to clinicians. | 60 days | 
| Number of Clinician-accepted of Recommendations as Measured by Tabulation | To assess the proportion of study pharmacist recommendations acted on by clinicians. | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYP 2C19, CYP 3A4, CYP 3A5, Home Care Agencies, Home Health Care Agencies, Home Health Care Nursing, Home Health Nurses, CYP 2D6, CYP 2C9