Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

NCT02120729 | Unknown DMC

• 1 other identifier: RUAN004090HE
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

Brief Summary

This Randomized Clinical Trial (RCT) compares outcomes in patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype status versus empiric "standard-of-care" psychotropic therapy. The hypothesis is that provision of medication based on the functional status of the patient's CYP2D6 enzyme inferred from genotype results within 48 hours of admission to treating clinicians will, through refined selection of psychotropic medication during hospitalization, decrease length of psychiatric hospitalization stay and decrease the rate of 30 day re-admission. The trial setting is the Hartford Hospital Institute of Living (IOL). The IOL operated the Clinical Evaluation and Monitoring System (CEMS), an innovative electronic messaging system developed by Co-Investigator Dr. J.W. Goethe. The Hartford Hospital Genetics Research Center (GRC) performs the genotype testing. CYP2D6 genotype analysis detects all known polymorphisms that result in an enzyme with sub-normal or supra-normal function. In this study, CEMS transmits clinically actionable guidance based on the patient's genotype to the clinician, advancing the medication alerts in real time. The RCT will test the effects of timely incorporation of medication recommendations based on CYP2D6 genotype into CEMS. The RCT randomizes patients to standard therapy (Group S) for whom CYP2D6 genetic information is determined but not transmitted to the treating clinician, allowing psychotropic therapy to be empirically determined, and to genetically guided therapy (Group G) where genotyping result and treatment recommendations are furnished via CEMS to the clinician within 48 hours of admission. For patients in Group G who are poor or rapid metabolizers, medications primarily metabolized by the CYP2D6 enzyme are proscribed. The primary outcome is hospital length of stay and the secondary outcome, the frequency of 30 day hospital readmission. Additional genetic stratification of both Group S and Group G will allow investigation of specific psychotropic usage. The expected benefits are (1) quantitative understanding of the effect of providing CYP2D6 pharmacogenetic information on length of hospitalization, 30 day readmission rate, and associated costs; and (2) objective benchmarking for the comparative effectiveness of CYP2D6 genotyping for guiding psychotropic therapy.

Conditions

Major Depressive Disorder

Keywords

Pharmacogenetics; CYP2D6 Mutations; Major Depressive Disorder; Psychiatric Inpatients; Length of Stay; 30 Day Readmission Rate; Psychiatric hospital inpatients

Outcome Measures

Primary Outcomes (1)

• Length of Hospitalization Stay

  Number of days hospitalized for the current psychiatric admission

  30 days following discharge from index hospitalization

Secondary Outcomes (1)

• Readmission to Psychiatric Hospital within 30 days

  30 days following discharge from index hospitalization

Study Arms (2)

Standard of Care

NO INTERVENTION

Patients assigned to standard-of-care pharmacotherapy, for whom CYP2D6 genotype is determined but not utilized to guide drug prescription and psychotropic therapy follows the institutional norm.

Genotype-guided Care

ACTIVE COMPARATOR

Patients assigned to genetically-guided pharmacotherapy, for whom CYP2D6 genotype is determined but not utilized to guide drug prescription as part of psychotropic therapy.

Other: Genotype-guided care

Interventions

Genotype-guided care OTHER

Pharmacogenetic alerts are furnished to the clinician within 2 days of admission. Buccal cell DNA is analyzed for 21 common CYP2D6 polymorphisms and results quantified into a drug metabolism reserve index to establish levels of sub-normal function (poor metabolizer) or supra-normal function (rapid metabolizer). For the estimated 50% of patients who are poor or rapid metabolizers, CEMS will proscribe medications which are major CYP2D6 substrates.

Genotype-guided Care

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged 18 y or older.
• Patients who have been admitted to the Institute of Living and having a diagnosis of major depressive disorder.
• The ability to understand the requirements of the study.
• The ability to comply with study procedures and protocol.
• A woman is eligible to enter the study if she is of child-bearing potential and not pregnant or nursing.

You may not qualify if:

• Children and adolescents
• Hospital admission within previous 30 d of current admission.
• History of dementia or Alzheimer's disease
• History of chronic kidney disease (CKD).
• Surgery within 6 wk.
• Ischemic stroke within 6 wk.
• Any history of hemorrhagic stroke or subarachnoid hemorrhage.
• Current enrollment in an investigational drug or device study that has not reached the time of the primary end point

Sponsors & Collaborators

• Hartford Hospital: lead
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (1)

Institute of Living at Hartford Hospital, Hartford Healthcare

Hartford, Connecticut, 06114, United States

Location

Related Publications (1)

• Ruano G, Szarek BL, Villagra D, Gorowski K, Kocherla M, Seip RL, Goethe JW, Schwartz HI. Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder. Biomark Med. 2013 Jun;7(3):429-39. doi: 10.2217/bmm.13.16.

  PMID: 23734807 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Gualberto Ruano, M.D., Ph.D.

  Hartford Hospital Genetics Research Center

  PRINCIPAL INVESTIGATOR

• John W Goethe, M.D. Retired

  Institute of Living, Hartford Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2014
• First Posted: April 23, 2014
• Study Start: March 1, 2014
• Primary Completion: August 1, 2018
• Study Completion: October 1, 2019
• Last Updated: February 12, 2019

Record last verified: 2019-02

Locations

US (1)