Omeprazole and Famotidine in Chronic Dysfunction of the Transplanted Kidney

NCT05061303 | Unknown

• 1 other identifier: 687/20
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to compare the effect of omeprazole and famotidine on the risk of developing chronic renal transplant dysfunction. For the study, it is planned to qualify 24 stabilized adult patients from 1-24 months after kidney transplantation, who will receive p.o. the standard, most commonly used triple immunosuppression regimen: tacrolimus, mycophenolate mofetil, prednisone and depending on the group p.o.: omeprazole 20 mg (group I) or famotidine 20 mg (group II). The material in the study will be blood, in which tacrolimus concentrations will be measured at the following time points: 0, 2h, 6h, 12h after drug administration, without taking omeprazole/famotidine and then the next day after taking the protective drug in same time points, without 12h. Sequentially routinely in the so-called point T0 before taking the drug (12 hours after the last dose) during follow-up visits at the Transplant Outpatient Clinic. Tacrolimus concentrations will be determined using the Chemiluminescent Microparticle Immuno Assay method. As standard, laboratory tests will be performed during follow-up visits. In addition, it is planned to assess titer of donor-specific antibodies at the time of qualification and then after 18 months, immunological profile (flow cytometry) at the time of qualification and then after 18 months, and concentration in serum and urine of a potential marker of progression and decrease in glomerular filtration - kidney injury molecule-1 at the time of qualification and then after 18 months. The obtained results will be correlated with the histopathological evaluation of the transplanted kidney in the case of organ biopsy performed on clinical indications. Comparative statistical analysis of drug concentration values will be carried out. Additionally, genetic tests will be performed to assess the patient's metabolic variant for CYP2C19. Due to the potential influence of omeprazole on the pharmacokinetics of tacrolimus, which may influence the process of chronic rejection of the transplanted kidney and drug toxicity, it seems important to study this hypothesis, as well as researching for therapeutic substances neutral to the above process. The use of famotidine in place of omeprazole may turn out more beneficial and safer for renal transplant patients. During follow-up visits at the Transplant Clinic at the Department and Clinic of Nephrology, Transplantology and Internal Diseases, changes in blood concentrations of tacrolimus are noticed. Related reasons are being looked for. The above study will confirm or reject the relationship of changes in tacrolimus levels with omeprazole. It is planned to present the results at a scientific conference. The research results will be published in a scientific journal.

Conditions

Kidney Rejection Transplant

Keywords

chronic kidney rejection process; tacrolimus; omeprazole; famotidine

Outcome Measures

Primary Outcomes (4)

• Assessment of the drug concentration in the blood

  The material in the study will be blood, in which tacrolimus concentrations will be measured at the following time points: 0, 2h, 6h, 12h after drug administration, without taking omeprazole/famotidine and then the next day after taking the protective drug in same time points, without 12h. Sequentially routinely in the so-called point T0 before taking the drug (12 hours after the last dose) during follow-up visits at the Transplant Outpatient Clinic.

  Sequentially routinely in the so-called point T0 before taking the drug (12 hours after the last dose) during follow-up visits at the Transplant Outpatient Clinic.

• Change from Baseline titer of donor-specific antibodies

  Change from Baseline donor-specific antibodies after 18 months.

  0, 6, 12, 18 Month

• Change from Baseline immunological profile (flow cytometry) - Th2 to Th1 ratio

  Change from Baseline immunological profile (flow cytometry) - Th2 to Th1 ratio after 18 months.

  0, 18 Month

• Change from Baseline concentration in serum and urine of a potential marker of progression and decrease in glomerular filtration - kidney injury molecule-.

  Change from Baseline concentration in serum and urine of a potential marker of progression and decrease in glomerular filtration - kidney injury molecule-1 after 9 and 18 months.

  0, 18 Month

Study Arms (2)

Group Omperazole

Patients will receive p.o. the standard, most commonly used triple immunosuppression regimen: tacrolimus, mycophenolate mofetil, prednisone and p.o. omeprazole 20 mg (group Omeprazole).

Other: Assessment of the drug concentration in the blood

Group Famotidine

Patients will receive p.o. the standard, most commonly used triple immunosuppression regimen: tacrolimus, mycophenolate mofetil, prednisone and p.o. famotidine 20 mg (group Famotidine).

Other: Assessment of the drug concentration in the blood

Interventions

Assessment of the drug concentration in the blood OTHER

The material in the study will be blood, in which tacrolimus concentrations will be measured at the following time points: 0, 2hours, 6hours, 12hours after drug administration, without taking omeprazole/famotidine and then the next day after taking the protective drug in same time points, without 12hours. Sequentially routinely in the so-called point T0 before taking the drug (12 hours after the last dose) during follow-up visits at the Transplant Outpatient Clinic.

Group Famotidine; Group Omperazole

Eligibility Criteria

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

Study Population

For the study, it is planned to qualify stabilized adult patients from 1-24 months after kidney transplantation, who will receive p.o. the standard, most commonly used triple immunosuppression regimen: tacrolimus, mycophenolate mofetil, prednisone and omeprazole 20 mg or famotidine 20 mg.

You may qualify if:

• receiving of p.o. the standard, most commonly used triple immunosuppression regimen: tacrolimus, mycophenolate mofetil, prednisone and omeprazole or famotidine,
• stabilized adult patients from 1-24 months after kidney transplantation

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead

Study Sites (1)

University Clinical Hospital in Poznan of the Poznan University of Medical Sciences

Poznan, 60-355, Poland

Location

Related Publications (12)

• Takahashi K, Yano I, Fukuhara Y, Katsura T, Takahashi T, Ito N, Yamamoto S, Ogawa O, Inui K. Distinct effects of omeprazole and rabeprazole on the tacrolimus blood concentration in a kidney transplant recipient. Drug Metab Pharmacokinet. 2007 Dec;22(6):441-4. doi: 10.2133/dmpk.22.441.

  PMID: 18159131 BACKGROUND

• Moreau C, Debray D, Loriot MA, Taburet AM, Furlan V. Interaction between tacrolimus and omeprazole in a pediatric liver transplant recipient. Transplantation. 2006 Feb 15;81(3):487-8. doi: 10.1097/01.tp.0000194861.59543.b9. No abstract available.

  PMID: 16477241 BACKGROUND

• Zhao W, Fakhoury M, Maisin A, Baudouin V, Storme T, Deschenes G, Jacqz-Aigrain E. Pharmacogenetic determinant of the drug interaction between tacrolimus and omeprazole. Ther Drug Monit. 2012 Dec;34(6):739-41. doi: 10.1097/FTD.0b013e318271b6e6.

  PMID: 23042259 BACKGROUND

• Hosohata K, Masuda S, Katsura T, Takada Y, Kaido T, Ogura Y, Oike F, Egawa H, Uemoto S, Inui K. Impact of intestinal CYP2C19 genotypes on the interaction between tacrolimus and omeprazole, but not lansoprazole, in adult living-donor liver transplant patients. Drug Metab Dispos. 2009 Apr;37(4):821-6. doi: 10.1124/dmd.108.025833. Epub 2009 Jan 12.

  PMID: 19139162 BACKGROUND

• Maguire M, Franz T, Hains DS. A clinically significant interaction between tacrolimus and multiple proton pump inhibitors in a kidney transplant recipient. Pediatr Transplant. 2012 Sep;16(6):E217-20. doi: 10.1111/j.1399-3046.2011.01559.x. Epub 2011 Aug 23.

  PMID: 21883747 BACKGROUND

• Boso V, Herrero MJ, Bea S, Galiana M, Marrero P, Marques MR, Hernandez J, Sanchez-Plumed J, Poveda JL, Alino SF. Increased hospital stay and allograft dysfunction in renal transplant recipients with Cyp2c19 AA variant in SNP rs4244285. Drug Metab Dispos. 2013 Feb;41(2):480-7. doi: 10.1124/dmd.112.047977. Epub 2012 Nov 21.

  PMID: 23175667 BACKGROUND

• Pascual J, Marcen R, Orea OE, Navarro M, Alarcon MC, Ocana J, Villafruela JJ, Burgos FJ, Ortuno J. Interaction between omeprazole and tacrolimus in renal allograft recipients: a clinical-analytical study. Transplant Proc. 2005 Nov;37(9):3752-3. doi: 10.1016/j.transproceed.2005.09.126.

  PMID: 16386527 BACKGROUND

• Peloso LJ, Faria PN, Bossolani MV, de Oliveira HB, Ferreira Filho SR. The serum concentration of tacrolimus after ingesting omeprazole: a pilot study. Transplantation. 2014 Sep 27;98(6):e63-4. doi: 10.1097/TP.0000000000000351. No abstract available.

  PMID: 25221905 BACKGROUND

• Mei S, Wang J, Chen D, Zhu L, Zhao M, Tian X, Hu X, Zhao Z. Simultaneous determination of cyclosporine and tacrolimus in human whole blood by ultra-high performance liquid chromatography tandem mass spectrometry and comparison with a chemiluminescence microparticle immunoassay. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 15;1087-1088:36-42. doi: 10.1016/j.jchromb.2018.04.028. Epub 2018 Apr 13.

  PMID: 29704799 BACKGROUND

• Shahbaz SK, Pourrezagholi F, Barabadi M, Foroughi F, Hosseinzadeh M, Ahmadpoor P, Nafar M, Yekaninejad MS, Amirzargar A. High expression of TIM-3 and KIM-1 in blood and urine of renal allograft rejection patients. Transpl Immunol. 2017 Aug;43-44:11-20. doi: 10.1016/j.trim.2017.07.002. Epub 2017 Jul 27.

  PMID: 28757398 BACKGROUND

• Miedziaszczyk M, Karczewski M, Idasiak-Piechocka I. The effect of the use of omeprazole versus famotidine on the kidney transplant function: a randomized controlled study. Sci Rep. 2025 Jan 13;15(1):1805. doi: 10.1038/s41598-025-85534-w.

  PMID: 39805983 DERIVED

• Miedziaszczyk M, Karczewski M, Grabowski T, Wolc A, Idasiak-Piechocka I. Assessment of omeprazole and famotidine effects on the pharmacokinetics of tacrolimus in patients following kidney transplant-randomized controlled trial. Front Pharmacol. 2024 Apr 4;15:1352323. doi: 10.3389/fphar.2024.1352323. eCollection 2024.

  PMID: 38638867 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: September 29, 2021
• Study Start: October 17, 2021
• Primary Completion: January 19, 2023
• Study Completion: June 30, 2024
• Last Updated: January 23, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)