Evaluating Pharmacogenomic Variants for Cardiology Therapeutics

Myocardial Infarction Clinical Trial

— CARES2  

Official title:

Evaluating Pharmacogenomic Variants for Cardiology Therapeutics: the Lighthouse Pilot (Association Between Genetic Variant Scores and P2Y12 Inhibitor Effects)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04702113
• Other study ID #: C03-002 DHR001
• Status: Completed
• Phase: N/A
• Start date: December 3, 2020
• Est. completion date: July 27, 2023

Study information

• Verified date: September 2023
• Source: Cipherome, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cipherome's Lighthouse is a clinical decision support tool that incorporates a patient's pharmacogenetic information to determine therapeutic strategy, including determining appropriate dosage or assessing the likelihood of toxicity of a therapeutic regimen.

Description:

The Lighthouse tool incorporates pharmacogenetic (PGx) variants from well-established, evidence-based guidelines to provide personalized drug response profile(s) to guide treatment decisions.

The patient specimen is genotyped using a proprietary, carefully curated pharmacogenetic variant panel to determine the individual's phenotype. The Lighthouse report (PGx findings) are provided to the clinician, and a notification is generated when the patient has a genotype with a deleterious drug-metabolizing phenotype.

Evaluating the South Texas community for the pilot project will enhance the understanding of the impact of genetic variants on individuals of Hispanic/Latino ancestry, especially as the variants pertain to the efficacy and safety of medications.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: July 27, 2023
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Subjects over 18 years of age, who are:

• On clopidogrel, prasugrel or ticagrelor after percutaneous stent

• Completed informed consent

Exclusion Criteria:

• Failure to provide informed consent.

• Lost to follow-up prior to 60 days.

Related Conditions & MeSH terms

• Bleeding
• Infarction
• Ischemic Stroke
• Myocardial Infarction
• Stent Thrombosis
• Thrombosis

Intervention

Diagnostic Test:
• Cipherome Lighthouse Pilot
Preemptive pharmacogenomic testing

Locations

Country	Name	City	State
United States	Doctors Hospital at Renaissance	Edinburg	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Cipherome, Inc.	DHR Health Institute for Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (15)

Claudio-Campos K, Duconge J, Cadilla CL, Ruano G. Pharmacogenetics of drug-metabolizing enzymes in US Hispanics. Drug Metab Pers Ther. 2015 Jun;30(2):87-105. doi: 10.1515/dmdi-2014-0023. — View Citation

Dean L. Prasugrel Therapy and CYP Genotype. 2017 Apr 10. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK425796/ — View Citation

Lee CR, Sriramoju VB, Cervantes A, Howell LA, Varunok N, Madan S, Hamrick K, Polasek MJ, Lee JA, Clarke M, Cicci JD, Weck KE, Stouffer GA. Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention. Circ Genom Precis Med. 2018 Apr;11(4):e002069. doi: 10.1161/CIRCGEN.117.002069. — View Citation

Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr, Halperin JL, Levine GN, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, Cigarroa JE, Curtis LH, Fleisher LA, Gentile F, Gidding S, Hlatky MA, Ikonomidis JS, Joglar JA, Pressler SJ, Wijeysundera DN. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Thorac Cardiovasc Surg. 2016 Nov;152(5):1243-1275. doi: 10.1016/j.jtcvs.2016.07.044. No abstract available. — View Citation

Limdi NA, Cavallari LH, Lee CR, Hillegass WB, Holmes AM, Skaar TC, Pisu M, Dillon C, Beitelshees AL, Empey PE, Duarte JD, Diaby V, Gong Y, Johnson JA, Graves J, Garbett S, Zhou Z, Peterson JF; Implementing GeNomics In pracTicE (IGNITE) Network Pharmacogenetic Working Group (IGNITE-PGx). Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data. Pharmacogenomics J. 2020 Oct;20(5):724-735. doi: 10.1038/s41397-020-0162-5. Epub 2020 Feb 11. — View Citation

Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010 Oct 27;304(16):1821-30. doi: 10.1001/jama.2010.1543. — View Citation

Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available. — View Citation

MEPS 2019. Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey. MEPS HC-197A: 2017. Prescribed Medicines File. July 2019.

Parks AL, Fang MC. Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding. Semin Thromb Hemost. 2017 Jul;43(5):514-524. doi: 10.1055/s-0037-1598061. Epub 2017 Mar 30. — View Citation

Pereira 2019. Pereira NL, Charanjit S, Rihal MD et al. Clopidogrel Pharmacogenetics. State-of-the-Art Review and the TAILOR-PCI Study. Circ Cardiovasc Interv. 2019:1-11.

Pereira INTV 2020. CC News Story, TAILOR-PCI: Genotype-guided Antiplatelet Therapy Post PCI Misses Mark. American Academy of Cardiology. Pulled 18 September 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/24/16/41/sat-9am-tailor-pci-clinical-implementation-clopidogrel-pharmacogenetics-acc-2020.

Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, Bell M, Bae JH, Jeong MH, Chavez I, Gordon P, Abbott JD, Cagin C, Baudhuin L, Fu YP, Goodman SG, Hasan A, Iturriaga E, Lerman A, Sidhu M, Tanguay JF, Wang L, Weinshilboum R, Welsh R, Rosenberg Y, Bailey K, Rihal C. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA. 2020 Aug 25;324(8):761-771. doi: 10.1001/jama.2020.12443. — View Citation

Python 2020. Python code Mersenne Twister core generator with a period of (219937 -1). The Python Standard Library / Numeric and Mathematical Modules / random - Generate pseudo-random numbers. https://docs.python.org/3/library/random.html

Wasfy JH, Strom JB, Waldo SW, O'Brien C, Wimmer NJ, Zai AH, Luttrell J, Spertus JA, Kennedy KF, Normand SL, Mauri L, Yeh RW. Clinical preventability of 30-day readmission after percutaneous coronary intervention. J Am Heart Assoc. 2014 Sep 26;3(5):e001290. doi: 10.1161/JAHA.114.001290. — View Citation

Yost GW, Puher SL, Graham J, Scott TD, Skelding KA, Berger PB, Blankenship JC. Readmission in the 30 days after percutaneous coronary intervention. JACC Cardiovasc Interv. 2013 Mar;6(3):237-44. doi: 10.1016/j.jcin.2012.10.015. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of the correlation of clinical factors (age, labs, medications) on predicting and preventing adverse drug reactions	Assess the correlation of clinical factors (age, liver function tests, concomitant medications, etc.) on predicting and preventing adverse drug reactions (ADRs).	Study pilot duration is 365 days (1 year)
Primary	Evaluation of aggregate costs	The cumulative direct medical cost (admissions, procedures, clinical visits, blood transfusions, drugs) of percutaneous insertion of stents (PCIs) and associated major adverse cardiovascular and cerebrovascular events (MACCE) including non-fatal myocardial infarction, non-fatal stroke, cardiovascular mortality, severe recurrent ischemia and stent thrombosis, and the costs of P2Y12 inhibitors and pharmacogenomic test costs.	Study pilot duration is 365 days (1 year)
Secondary	Reduction of treatment failures	Reduced treatment failures within 30, 60, 90 days, and 12 months of receiving clopidogrel in participants with reduced function alleles (CYP2C19 *2 or *3)	Study pilot duration is 365 days (1 year)
Secondary	Reduction of major or minor bleeding events	Reduced major or minor bleeding events within 30, 60, 90 days, and 12 months of receiving clopidogrel in participants with increased function alleles (CYP2C19 *17)	Study pilot duration is 365 days (1 year)

External Links

•   Change is coming in 2018-be prepared!
•   Clinical Pharmacogenetics Implementation Consortium (CPIC) 2020
•   FDA ADR 2020
•   FDA ADR 2020
•   Sauer 2017. PCI Within the Context of the Episode Payment Model
•   Simmons 2018. Clearwater Corporation, "Letter to HHS Physician Focused Payment Model Technical Advisory Committee"
•   TAILOR PCI
•   TAILOR PCI
•   Truesdale 2017. Truesdale K., Corazon, Inc. "Change is coming in 2018-be prepared!