Clinical trial NCT01970709: Diagnosing Adverse Drug Reactions Registry
Official title: DART Registry: Diagnosing Adverse Drug Reactions Registry
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Genetics of Drug Metabolism
Keywords: Adverse Drug Reactions
Emergency Department Visits
Hospitalizations
Pharmacogenomic
Lead sponsor: Renaissance RX
Sponsor class: INDUSTRY
Collaborators: name: Syntactx
First posted: 2013-10-28
Enrollment: 250000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female subjects over the age of 18, taking three or more medications, two of which are metabolized by the CYP450 pathway.

Brief summary: This multicenter Registry is to assess whether the use of pharmacogenomic data results in a meaningful change in a subject's drug or dose regimen. In addition, the Registry will evaluate the relationship between adverse drug reactions (ADR) and genotype and assess resource utilization (emergency department visits and hospitalizations) associated with ADR.


Eligibility criteria: Inclusion Criteria:

* Subject has care coordinated at the treating physician's outpatient clinic;
* Subject has provided written informed consent;
* Subject is taking at least three (3) regularly scheduled medications, excluding as needed (PRN) medications, over the counter medications and nutritional supplements; two (2) of which are known to be affected by genetic allelic variation.
* Subject's treating physician has a clinical suspicion that the subject is experiencing adverse signs or symptoms related to a prescribed medication or is not achieving the intended effect from the medication.

Exclusion Criteria:

* Subject has a history of chronic renal dysfunction, Chronic Kidney Disease Stage 4 or 5;
* Subject has a history of abnormal hepatic function within the last 2 years (INR \>1.2 not attributable to anticoagulant medications, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) \>1.5x normal, or suspected cirrhosis);
* Subject has a history of malabsorption (short gut syndrome);
* Subject has a history of any gastric or small bowel surgery;
* Subject is currently hospitalized;
* Subject is currently being treated with intravenous medication;
* Subject underwent prior pharmacogenomic testing with results reported within the last 12 months.

Subjects may be eligible within 60 days from the date of pharmacogenomic testing.

Primary outcomes:
measure: Occurrence of meaningful change in drug regimen
timeFrame: 60 days
Secondary outcomes:
measure: Change in the regimen of drugs controlled by genes of interest over the 12 months prior to enrollment and change in the regimen of drugs controlled by genes of interest over the 60 days following receipt of pharmacogenetic test results.
timeFrame: 60 days
measure: Number of ADR per month over the 12 months prior to enrollment and number of ADR per month over the 60 days following receipt of pharmacogenomic test results.
timeFrame: 60 days
measure: Frequency of genome-based PharmD recommendations to alter drug or dose.
timeFrame: 60 days
measure: Emergency department visits and hospitalizations
timeFrame: 60 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Edwards Lake Medical Center
state: Alabama
city: Glendale
country: United States
facility: Gerald Harris MD
state: Arizona
city: Peoria
country: United States
facility: Holland Center for Family Health
state: Arizona
city: Phoenix
country: United States
facility: AZ Pain Center
state: Arizona
city: Los Angeles
country: United States
facility: Olga Voroshilovsky
state: California
city: Pasadena
country: United States
facility: Institute for Regenerative Medicine and Clinical Research
state: California
city: Boulder
country: United States
facility: Boulder Medical Center
state: Colorado
city: Avon
country: United States
facility: Prime Healthcare - Anthony Roselli MD
state: Connecticut
city: Washington
country: United States
facility: Washington Pain Center
state: District of Columbia
city: Doral
country: United States
facility: Continental Research Network
state: Florida
city: Miami
country: United States
facility: Latin Foundation for Health
state: Florida
city: Stuart
country: United States
facility: Primary Care Associates, P.A.
state: Florida
city: Columbus
country: United States
facility: Roman Medical Group
state: Georgia
city: Hampton
country: United States
facility: Wellness Medicine
state: Georgia
city: Macon
country: United States
facility: Ocmulgee Physicians
state: Georgia
city: Macon
country: United States
facility: Macon Family Health Center Inc.
state: Georgia
city: Rome
country: United States
facility: Your Personal Physician
state: Georgia
city: Rome
country: United States
facility: Valley Health Care
state: Georgia
city: Snellville
country: United States
facility: Dr. B. Abraham PC
state: Georgia
city: Statesboro
country: United States
facility: Candler Internal Medicine
state: Georgia
city: Orland Park
country: United States
facility: Primary Health Associates
state: Illinois
city: Lexington
country: United States
facility: Women's Care Center
state: Kentucky
city: Grandville
country: United States
facility: Healthy Heart Cardiology
state: Michigan
city: Southfield
country: United States
facility: Heart Cardiology Consultants
state: Michigan
city: Elizabeth
country: United States
facility: Union Square Medical Associates, PC
state: New Jersey
city: Lyndhurst
country: United States
facility: United Medical PC
state: New Jersey
city: Alamogordo
country: United States
facility: Internal Medicine Specialists of Alamogordo, P.C.
state: New Mexico
city: Albuquerque
country: United States
facility: Lovelace Rehabilitation Hospital
state: New Mexico
city: Albuquerque
country: United States
facility: Sage Neuroscience Center
state: New Mexico
city: Albuquerque
country: United States
facility: Geriatrics Associates, PAC
state: New Mexico
city: Las Cruces
country: United States
facility: Isabel C Vigil MD
state: New Mexico
city: Charlotte
country: United States
facility: Larry F Berman MD PC
state: North Carolina
city: Durham
country: United States
facility: Lakewood Pediatrics and Family Medicine
state: North Carolina
city: Gastonia
country: United States
facility: Carolina Urology Partners
state: North Carolina
city: Greensboro
country: United States
facility: Carolina Neurosurgery and Spine Associates
state: North Carolina
city: Columbus
country: United States
facility: Comprehensive Pain Center
state: Ohio
city: Columbus
country: United States
facility: Knightsbridge Internal Medicine and Cardiology Associates, Inc
state: Ohio
city: Columbus
country: United States
facility: Gateway Health and Wellness LLC
state: Ohio
city: Mansfield
country: United States
facility: Robert E Barkett Jr MD
state: Ohio
city: Marion
country: United States
facility: Midwestern Internal Medicine Associates (MIMA)
state: Ohio
city: Reynoldsburg
country: United States
facility: Stonegate Family Health
state: Ohio
city: Tallmadge
country: United States
facility: Primary Care Associates - Unity
state: Ohio
city: Easton
country: United States
facility: Easton Cardiovascular Associates
state: Pennsylvania
city: Greenville
country: United States
facility: Carolina Center For Advanced Management Of Pain
state: South Carolina
city: Sumter
country: United States
facility: Colonial Family Practice
state: South Carolina
city: Sumter
country: United States
facility: Palmetto Adult Medicine
state: South Carolina
city: Oak Ridge
country: United States
facility: Parkway Cardiology Associates
state: Tennessee
city: Fort Worth
country: United States
facility: Mark A. Sanders, DO
state: Texas
city: Emporia
country: United States
facility: Emporia Medical Associates
state: Virginia
Study officials:
References:
citation: Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenboom WP, Somers A, Rajkumar C, Bernabei R, van der Cammen TJ. Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score. Arch Intern Med. 2010 Jul 12;170(13):1142-8. doi: 10.1001/archinternmed.2010.153.
citation: Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998 Apr 15;279(15):1200-5. doi: 10.1001/jama.279.15.1200.
citation: Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053.
citation: Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007 Jul 14;370(9582):185-191. doi: 10.1016/S0140-6736(07)61092-7.
citation: Epstein RS, Moyer TP, Aubert RE, O Kane DJ, Xia F, Verbrugge RR, Gage BF, Teagarden JR. Warfarin genotyping reduces hospitalization rates results from the MM-WES (Medco-Mayo Warfarin Effectiveness study). J Am Coll Cardiol. 2010 Jun 22;55(25):2804-12. doi: 10.1016/j.jacc.2010.03.009. Epub 2010 Apr 8.
citation: Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. N Engl J Med. 2011 Mar 24;364(12):1144-53. doi: 10.1056/NEJMra1010600. No abstract available.
citation: Aronson JK. Adverse drug reactions--no farewell to harms. Br J Clin Pharmacol. 2007 Feb;63(2):131-5. doi: 10.1111/j.1365-2125.2006.02860.x. No abstract available.
citation: Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000 Oct 7;356(9237):1255-9. doi: 10.1016/S0140-6736(00)02799-9.
citation: Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, Milligan PE, Grice G, Lenzini P, Rettie AE, Aquilante CL, Grosso L, Marsh S, Langaee T, Farnett LE, Voora D, Veenstra DL, Glynn RJ, Barrett A, McLeod HL. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008 Sep;84(3):326-31. doi: 10.1038/clpt.2008.10. Epub 2008 Feb 27.
citation: International Warfarin Pharmacogenetics Consortium; Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19;360(8):753-64. doi: 10.1056/NEJMoa0809329.
citation: Garcia DA, Lopes RD, Hylek EM. New-onset atrial fibrillation and warfarin initiation: high risk periods and implications for new antithrombotic drugs. Thromb Haemost. 2010 Dec;104(6):1099-105. doi: 10.1160/TH10-07-0491. Epub 2010 Sep 30.
citation: Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL. A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing. Pharmacoeconomics. 2010;28(1):61-74. doi: 10.2165/11318240-000000000-00000.
citation: Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011 Mar;89(3):464-7. doi: 10.1038/clpt.2010.279. Epub 2011 Jan 26.
citation: Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, Seger DL, Shu K, Federico F, Leape LL, Bates DW. Adverse drug events in ambulatory care. N Engl J Med. 2003 Apr 17;348(16):1556-64. doi: 10.1056/NEJMsa020703.
citation: Huhtakangas J, Tetri S, Juvela S, Saloheimo P, Bode MK, Hillbom M. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke. 2011 Sep;42(9):2431-5. doi: 10.1161/STROKEAHA.111.615260. Epub 2011 Jul 28.