Evaluating Pharmacogenomic Variants for Cardiology Therapeutics

NCT04702113 | Completed DMC

• 1 other identifier: C03-002 DHR001
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Thrombosis; Stent Thrombosis; Bleeding; Myocardial Infarction; Ischemic Stroke

Keywords

Stent Thrombosis; Major Adverse Cardiovascular and Cerebrovascular Events (MACCE)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Reduction of treatment failures

  Study pilot duration is 365 days (1 year)

• Reduction of major or minor bleeding events

  Study pilot duration is 365 days (1 year)

Other Outcomes (1)

• Assessment of the correlation of clinical factors (age, labs, medications) on predicting and preventing adverse drug reactions

  Study pilot duration is 365 days (1 year)

Study Arms (2)

Conventional Therapy (Controls)

NO INTERVENTION

Treatment with clopidogrel and no pre-emptive genotyping

Genotype-guided therapy (experimental)

EXPERIMENTAL

1. Treatment with clopidogrel 75 mg daily for non-carriers 2. Treatment with ticagrelor 90 mg twice daily for carriers

Diagnostic Test: Cipherome Lighthouse Pilot

Interventions

Cipherome Lighthouse Pilot DIAGNOSTIC_TEST

Preemptive pharmacogenomic testing

Genotype-guided therapy (experimental)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects over 18 years of age, who are:
• On clopidogrel, prasugrel or ticagrelor after percutaneous stent
• Completed informed consent

You may not qualify if:

• Failure to provide informed consent.
• Lost to follow-up prior to 60 days.

Sponsors & Collaborators

• Cipherome, Inc.: lead
• DHR Health Institute for Research and Development: collaborator

Study Sites (1)

Doctors Hospital at Renaissance

Edinburg, Texas, 78539, United States

Location

Related 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.

  PMID: 25431893 BACKGROUND

• Dean L, Kane M. Prasugrel Therapy and CYP Genotype. 2017 Apr 10 [updated 2024 Oct 15]. 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/

  PMID: 28520385 BACKGROUND

• 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.

  PMID: 29615454 BACKGROUND

• 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.

  PMID: 27751237 BACKGROUND

• 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.

  PMID: 32042096 BACKGROUND

• 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.

  PMID: 20978260 BACKGROUND

• 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.

  PMID: 21670242 BACKGROUND

• 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.

  PMID: 28359135 BACKGROUND

• 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.

  PMID: 32840598 BACKGROUND

• 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.

  PMID: 25261531 BACKGROUND

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

  BACKGROUND

• Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, Goodman SG, Weinshilboum RM, Wang L, Baudhuin LM, Lerman A, Hasan A, Iturriaga E, Fu YP, Geller N, Bailey K, Farkouh ME. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019 Apr;12(4):e007811. doi: 10.1161/CIRCINTERVENTIONS.119.007811.

  PMID: 30998396 BACKGROUND

• 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.

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 23517834 BACKGROUND

Related Links

• 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"
• Truesdale 2017. Truesdale K., Corazon, Inc. "Change is coming in 2018-be prepared!
• Change is coming in 2018-be prepared!
• TAILOR PCI
• TAILOR PCI

MeSH Terms

Conditions

Thrombosis; Hemorrhage; Myocardial Infarction; Ischemic Stroke

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Necrosis; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Herschl Silberman, MD

  DHR Health

  PRINCIPAL INVESTIGATOR

• Humberto Mochizu Kitamayo, MD

  DHR Health

  STUDY DIRECTOR

• Yetunde O Kare Opaneye, MD

  DHR Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label study.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There will be two study arms: 1. Conventional therapy (controls)-treatment with clopidogrel and no pre-emptive genotyping 2. Genotype-guided therapy (experimental)

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 8, 2021
• Study Start: December 3, 2020
• Primary Completion: July 26, 2023
• Study Completion: July 27, 2023
• Last Updated: September 29, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)