Diagnosing Adverse Drug Reactions Registry

Genetics of Drug Metabolism Clinical Trial

— DART  

Official title:

DART Registry: Diagnosing Adverse Drug Reactions Registry

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01970709
• Other study ID #: 2013-101
• Status: Active, not recruiting
• Phase: N/A
• First received: October 22, 2013
• Last updated: March 18, 2015
• Start date: November 2013

Study information

• Verified date: March 2015
• Source: Renaissance RX
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250000
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Observational Model: Cohort

Related Conditions & MeSH terms

• Drug-Related Side Effects and Adverse Reactions
• Genetics of Drug Metabolism

Locations

Country	Name	City	State
United States	Internal Medicine Specialists of Alamogordo, P.C.	Alamogordo	New Mexico
United States	Geriatrics Associates, PAC	Albuquerque	New Mexico
United States	Lovelace Rehabilitation Hospital	Albuquerque	New Mexico
United States	Sage Neuroscience Center	Albuquerque	New Mexico
United States	Prime Healthcare - Anthony Roselli MD	Avon	Connecticut
United States	Edwards Lake Medical Center	Birmingham	Alabama
United States	Boulder Medical Center	Boulder	Colorado
United States	Larry F Berman MD PC	Charlotte	North Carolina
United States	Comprehensive Pain Center	Columbus	Ohio
United States	Gateway Health and Wellness LLC	Columbus	Ohio
United States	Knightsbridge Internal Medicine and Cardiology Associates, Inc	Columbus	Ohio
United States	Roman Medical Group	Columbus	Georgia
United States	Continental Research Network	Doral	Florida
United States	Lakewood Pediatrics and Family Medicine	Durham	North Carolina
United States	Easton Cardiovascular Associates	Easton	Pennsylvania
United States	Union Square Medical Associates, PC	Elizabeth	New Jersey
United States	Emporia Medical Associates	Emporia	Virginia
United States	Mark A. Sanders, DO	Fort Worth	Texas
United States	Carolina Urology Partners	Gastonia	North Carolina
United States	Gerald Harris MD	Glendale	Arizona
United States	Healthy Heart Cardiology	Grandville	Michigan
United States	Carolina Neurosurgery and Spine Associates	Greensboro	North Carolina
United States	Carolina Center For Advanced Management Of Pain	Greenville	South Carolina
United States	Wellness Medicine	Hampton	Georgia
United States	Isabel C Vigil MD	Las Cruces	New Mexico
United States	Women's Care Center	Lexington	Kentucky
United States	Olga Voroshilovsky	Los Angeles	California
United States	United Medical PC	Lyndhurst	New Jersey
United States	Macon Family Health Center Inc.	Macon	Georgia
United States	Ocmulgee Physicians	Macon	Georgia
United States	Robert E Barkett Jr MD	Mansfield	Ohio
United States	Midwestern Internal Medicine Associates (MIMA)	Marion	Ohio
United States	Latin Foundation for Health	Miami	Florida
United States	Parkway Cardiology Associates	Oak Ridge	Tennessee
United States	Primary Health Associates	Orland Park	Illinois
United States	Institute for Regenerative Medicine and Clinical Research	Pasadena	California
United States	Holland Center for Family Health	Peoria	Arizona
United States	AZ Pain Center	Phoenix	Arizona
United States	Stonegate Family Health	Reynoldsburg	Ohio
United States	Valley Health Care	Rome	Georgia
United States	Your Personal Physician	Rome	Georgia
United States	Dr. B. Abraham PC	Snellville	Georgia
United States	Heart Cardiology Consultants	Southfield	Michigan
United States	Candler Internal Medicine	Statesboro	Georgia
United States	Primary Care Associates, P.A.	Stuart	Florida
United States	Colonial Family Practice	Sumter	South Carolina
United States	Palmetto Adult Medicine	Sumter	South Carolina
United States	Primary Care Associates - Unity	Tallmadge	Ohio
United States	Washington Pain Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Renaissance RX	Syntactx

Country where clinical trial is conducted

United States, 

References & Publications (15)

Aronson JK. Adverse drug reactions--no farewell to harms. Br J Clin Pharmacol. 2007 Feb;63(2):131-5. — View 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. — View Citation

Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000 Oct 7;356(9237):1255-9. — View 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. — View 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. Erratum in: Clin Pharmacol Ther. 2008 Sep;84(3):430. — View 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. — View 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. Review. — View 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. — View 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. Erratum in: N Engl J Med. 2009 Oct 15;361(16):1613. Dosage error in article text. — View 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. — View Citation

Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007 Jul 14;370(9582):185-91. Review. — View 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. — View 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. — View 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. — View 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. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of meaningful change in drug regimen	The primary endpoint of the study is the binary occurrence of meaningful change in drug regimen, defined in each subject when: A genotype known to affect a drug the subject is taking is identified, and; The subject's treating physician makes at least one drug regimen change in concordance with the PharmD recommendations.	60 days	No
Secondary	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.		60 days	No
Secondary	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.		60 days	No
Secondary	Frequency of genome-based PharmD recommendations to alter drug or dose.		60 days	No
Secondary	Emergency department visits and hospitalizations	Emergency department visits over the 12 months prior to enrollment, emergency department visits over the 60 days following receipt of test results, hospitalizations over the 12 months prior to enrollment, and hospitalizations over the 60 days following receipt of test results.	60 days	No