Effect of the CYP2C19 Polymorphism in Helicobacter Pylori Eradication

NCT03650543 | Completed Phase 4 DMC

• 2 other identifiers: 0000455412010U80401200
• Study Type: interventional
• Target: 133
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Triple therapy efficacy against Helicobacter pylori is low worldwide, thus alternatives must be sought to improve eradication. Aim: To determine CYP2C19 genetic polymorphism effect on H. pylori eradication. Methods: A randomized single blinded clinical trial including 133 patients was carried-out. H. pylori infection was confirmed by histology and microbiological test. Antibiotic susceptibility to amoxicillin and clarithromycin was performed to avoid confusion bias in analysis results. CYP2C19 polymorphism "asterisk" \*1, "asterisk"\*2 and "asterisk" \*3 was analyzed by Real time PCR (Roche ®), and nested PCR for CYP2C19 "asterisk" \*17 polymorphism. Participants were randomized into two groups for different H. pylori therapies, one with standard omeprazole doses and another with omeprazole doses depending on CYP2C19 polymorphism. H. pylori eradicating was verified by stool antigen testing (Meridian ®). The general results was analysis by statistical computer program and the effectiveness of each therapy was analyzed by intention to treat (ITT) and by protocol (PP). The study allowed to know the prevalence of the main polymorphisms of CYP2C19 in Bogotá-Colombia, also allowed to know the effectivenesses of the two therapies evaluated for H. pylori infection. Additionally, the importance of personalized medicine in H. pylori eradication therapy was known.

Conditions

CYP2C19 Polymorphism; H.Pylori Infection; Therapy

Outcome Measures

Primary Outcomes (1)

• Effectiveness of each therapy by protocol (PP)

  Percentage

  through study completion an average of 3 years

Secondary Outcomes (1)

• Effectiveness of each therapy by intention to treat (ITT)

  through study completion an average of 3 years

Other Outcomes (6)

• Gender

  through study completion an average of 3 years

• Weight

  through study completion an average of 3 years

• Height

  through study completion an average of 3 years

Study Arms (2)

amoxicillin clarithromycin omeprazole 1

EXPERIMENTAL

This group received triple standard therapy with standard doses of omeprazole. 20 mg "omeprazole" before breakfast and before dinner. 500 mg "clarithromycin" after breakfast and after dinner and 1 g "amoxicillin" after breakfast and after dinner for 10 days.

Drug: amoxicillin clarithromycin omeprazole 1

amoxicillin clarithromycin omeprazole 2

EXPERIMENTAL

This group received triple standard therapy, using 500 mg "clarithromycin" after breakfast and after dinner and 1 g "amoxicillin" after breakfast and after dinner for 10 days in addition with "omeprazole" but "omeprazole" doses were prescribed according to CYP2C19 genotype as a follows: a) Patients with CYP2C19 \*1/\*1 genotype (Early and ultrarapid Metabolizer): 40mg "omeprazole" before breakfast and before dinner. b) Patients with CYP2C19 \*1/\*2 or \*1/\*3 genotype (Intermediate Metabolizer): 20mg "omeprazole" before breakfast, 20mg before lunch and 20mg before dinner. c) Patients with CYP2C19 \*2/\*2 (Poor Metabolizer): 20mg "omeprazole" before breakfast and 20 mg before dinner.

Drug: amoxicillin clarithromycin omeprazole 2

Interventions

amoxicillin clarithromycin omeprazole 1 DRUG

Patients in this received triple standard therapy for eradication of H.pylori with standard doses of proton pump inhibitor (omeprazole), in combination with amoxicillin and clarithromycin in absence of antibiotic resistance.

Also known as: Conventional therapy, Group 1

amoxicillin clarithromycin omeprazole 1

amoxicillin clarithromycin omeprazole 2 DRUG

The treatment for patients in this group was prescribing triple standard therapy for H.pylori eradication with amoxicillin and clarithromycin in absence of antibiotic resistance but with different doses of proton pump inhibitor (omeprazole) according to CYP2C19 genotype in each patients.

Also known as: Personalized therapy, Group 2

amoxicillin clarithromycin omeprazole 2

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with functional dyspepsia or peptic ulcers
• Subjects between the ages of 19 and 70 years old
• Subjects who were referred for upper endoscopy, and had not received previous H. pylori eradication treatment within the last six months.
• Subjects who had not received anti-secreting acid, bismuth or antibiotics for other diseases 15 days before the endoscopy.
• For the study, only patients with sensitive isolates of H.pylori to amoxicillin and clarithromycin were included.

You may not qualify if:

• Patients with serious comorbidities.
• Pregnant women.
• Patients allergic to the medications used in this study.

Sponsors & Collaborators

• Javeriana University: lead
• Universidad Nacional de Colombia: collaborator

Related Publications (16)

• Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008 Jun;5(6):321-31. doi: 10.1038/ncpgasthep1138. Epub 2008 Apr 29.

  PMID: 18446147 BACKGROUND

• Sapone A, Vaira D, Trespidi S, Perna F, Gatta L, Tampieri A, Ricci C, Cantelli-Forti G, Miglioli M, Biagi GL, Paolini M. The clinical role of cytochrome p450 genotypes in Helicobacter pylori management. Am J Gastroenterol. 2003 May;98(5):1010-5. doi: 10.1111/j.1572-0241.2003.07427.x.

  PMID: 12809821 BACKGROUND

• Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Ikuma M, Ishizaki T, Hishida A. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter. 2007 Aug;12(4):317-23. doi: 10.1111/j.1523-5378.2007.00508.x.

  PMID: 17669104 BACKGROUND

• Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori Infection. Gastroenterol Clin North Am. 2010 Sep;39(3):465-80. doi: 10.1016/j.gtc.2010.08.007.

  PMID: 20951912 BACKGROUND

• Scott D, Weeks D, Melchers K, Sachs G. The life and death of Helicobacter pylori. Gut. 1998 Jul;43 Suppl 1(Suppl 1):S56-60. doi: 10.1136/gut.43.2008.s56.

  PMID: 9764042 BACKGROUND

• Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet. 2005 Jun;20(3):153-67. doi: 10.2133/dmpk.20.153.

  PMID: 15988117 BACKGROUND

• Chaudhry AS, Kochhar R, Kohli KK. Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors. Indian J Med Res. 2008 Jun;127(6):521-30.

  PMID: 18765869 BACKGROUND

• Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010 Mar;69(3):222-30. doi: 10.1111/j.1365-2125.2009.03578.x.

  PMID: 20233192 BACKGROUND

• Furuta T, Sugimoto M, Shirai N, Ishizaki T. CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor. Pharmacogenomics. 2007 Sep;8(9):1199-210. doi: 10.2217/14622416.8.9.1199.

  PMID: 17924835 BACKGROUND

• Isaza C, Henao J, Martinez JH, Sepulveda Arias JC, Beltran L. Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals. BMC Clin Pharmacol. 2007 Jul 11;7:6. doi: 10.1186/1472-6904-7-6.

  PMID: 17623107 BACKGROUND

• Arevalo-Galvis A, Trespalacios-Rangell AA, Otero W, Mercado-Reyes MM, Poutou-Pinales RA. Prevalence of cagA, vacA, babA2 and iceA genes in H. pylori strains isolated from Colombian patients with functional dyspepsia. Pol J Microbiol. 2012;61(1):33-40.

  PMID: 22708344 BACKGROUND

• Baldwin RM, Ohlsson S, Pedersen RS, Mwinyi J, Ingelman-Sundberg M, Eliasson E, Bertilsson L. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol. 2008 May;65(5):767-74. doi: 10.1111/j.1365-2125.2008.03104.x. Epub 2008 Feb 20.

  PMID: 18294333 BACKGROUND

• Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials. PLoS One. 2013 Apr 30;8(4):e62162. doi: 10.1371/journal.pone.0062162. Print 2013.

  PMID: 23646118 BACKGROUND

• Sugimoto M, Furuta T. Efficacy of tailored Helicobacter pylori eradication therapy based on antibiotic susceptibility and CYP2C19 genotype. World J Gastroenterol. 2014 Jun 7;20(21):6400-11. doi: 10.3748/wjg.v20.i21.6400.

  PMID: 24914361 BACKGROUND

• Arevalo-Galvis A, Otero-Regino WA, Ovalle-Celis GN, Rodriguez-Gomez ER, Trespalacios-Rangel AA. Prevalence of CYP2C19 polymorphism in Bogota, Colombia: The first report of allele *17. PLoS One. 2021 Jan 27;16(1):e0245401. doi: 10.1371/journal.pone.0245401. eCollection 2021.

  PMID: 33503046 DERIVED

• Arevalo Galvis A, Trespalacios Rangel AA, Otero Regino W. Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first-line triple therapy. Helicobacter. 2019 Jun;24(3):e12574. doi: 10.1111/hel.12574. Epub 2019 Mar 11.

  PMID: 30859680 DERIVED

Study Officials

• Alba Alicia Trespalacios Rangel, Ph.D

  Pontificia Universidad Javeriana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Masking Details: The mean masking was the treating Gastroenterologist doctor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Bacteriologist

Model Details: A randomized single - blinded Clinical Trial conducted from 2012 to 2015 in Bogotá, Colombia. The aim was studying the effectiveness of triple therapy for H. pylori with amoxicillin, clarithromycin and standard dose of omeprazole versus amoxicillin, clarithromycin with dose of omeprazole according to CYP2C19 polymorphisms was studied, the subjects were allocated to a treatment regimen according to a randomized crossover sequence, provided by a computer-generated randomization list. Patients were contacted by telephone for assigned an appointment for treatment delivery according to the assigned group.

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 28, 2018
• Study Start: September 10, 2012
• Primary Completion: August 8, 2015
• Study Completion: August 8, 2015
• Last Updated: August 28, 2018

Record last verified: 2018-08