Esomeprazole or Pantoprazole in Renal Transplantation

The Effect of Esomeprazole Versus Pantoprazole on Serum Cyclosporine Levels and Renal Function in Stable Kidney Transplant Recipients: A Randomized Clinical Trial

prospective, parallel, open-label clinical trial was performed on forty-seven adult renal transplant recipients receiving immunosuppressive therapy with CsA doses adjusted to attain trough concentrations of 100-150 μg/L, mycophenolate mofetil (MMF) at 750 mg q12 hr and prednisolone at 5 mg daily randomized into two groups, which received esomeprazole or pantoprazole at the same dose (40 mg once daily). To compare the influence of pantoprazole and esomeprazole on serum cyclosporine (CsA) levels in stable renal transplant recipients.Cyclosporine (C0), renal function and complete blood count were measured at baseline and for 6 months. Main outcome measures Clinical signs of rejection and renal function decline, assessed by serum creatinine elevations, caused by CsA level variations in either of the study groups.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant; Complications
• Intervention / Treatment: Drug: Esomeprazole 40 mg; Drug: Pantoprazole 40mg

Detailed Description

Study design and settings: This study is a prospective, single-centre, randomized, parallel, open-label 1:1 consecutive clinical trial of renal transplant recipients, with a follow-up 6 months; the study included an esomeprazole group (n = 25 at study completion) and a pantoprazole group (n = 22 at study completion). The study was conducted in the renal transplantation unit of the Nasser Institute in Cairo, Egypt.

Eighty renal transplant recipients were screened for eligibility. The sample size was determined by a power calculation using G power software version 3.0.10; the selected sample size showed an actual power of 0.95, α = 0.5 and an effect size of 0.8 for C0 levels of CsA and an actual power of 0.95, α = 0.5 and an effect size of 0.44 for serum creatinine levels.The participants were randomly assigned to one of two groups by single randomization. Each group received PPI therapy with a 40 mg/day dose of either esomeprazole (Ezogast; Copad Pharma, Cairo, Egypt) in group I (n = 25 at study completion) or pantoprazole (Pantoprazole; Pharo Pharma, Alexandria, Egypt) in group II (n = 22 at study completion).

In addition, participants continued to receive the immunosuppressant combination of CsA (Sandimmune; Novartis, East Hanover, NJ, USA), MMF (Cellcept; Roche, Basel, Switzerland) and the corticosteroid prednisolone (Solupred; Sanofi Aventis, Tours, France).

Administration: CsA was administered in two divided doses adjusted to achieve a C0 of 100-150 µg/L according to the transplantation centre protocol for maintenance blood CsA levels. The morning was dose separated from PPIs by at least 15 minutes, with MMF administered at 750 mg q12 hr and prednisolone administered at 5 mg daily. Each group received 40 mg/day PPI therapy on an empty stomach, and all medications were taken orally.

Renal function tests Included Parameter Assay Kits Serum creatinine QuantiChrom creatinine assay kit Blood urea nitrogen QuantiChrom urea assay kit Serum uric acid QuantiChrom uric acid assay kit Complete blood count measurements included Parameter Assay Kits Haemoglobin White blood cells (WBCs) UniCel DxH 800 Coulter Cellular Analysis System Platelets

Whole-blood C0 values in morning samples were determined spectrophotometrically using the CEDIA Cyclosporine PLUS Assay and the Indiko Plus Benchtop Analyzer (Thermo Fisher Scientific, Waltham, MA, USA)

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• stable adult renal transplant recipients
• participants continued the same maintenance triple immunosuppressive therapy,
• triple immunosuppressive therapy was received for at least 3 years prior to the study
• transplanted 5 years before the start of the study

Exclusion Criteria:

• Paediatric patients
• patients > 65 years old
• multi-organ transplant recipients
• pregnant or lactating patients
• patients with malignancies,
• patients with active infection or inflammation
• pre-transplant GI tract disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group I; Esomeprazole 40 mg capsules once daily for 6 months	Drug: Esomeprazole 40 mg; Esomeprazole 40 mg In addition, the immunosuppressant combination of CsA (Sandimmune; Novartis, East Hanover, NJ, USA), MMF (Cellcept; Roche, Basel, Switzerland) and the corticosteroid prednisolone (Solupred; Sanofi Aventis, Tours, France).; Other Names: Ezogast
Active Comparator: group II; Pantoprazole 40 mg tablets once daily for 6 months	Drug: Pantoprazole 40mg; Pantoprazole 40 mg In addition, the immunosuppressant combination of CsA (Sandimmune; Novartis, East Hanover, NJ, USA), MMF (Cellcept; Roche, Basel, Switzerland) and the corticosteroid prednisolone (Solupred; Sanofi Aventis, Tours, France).; Other Names: Pantoprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum CsA (C0) level	trough CsA serum levels in µg/L	up to 30 weeks from date of randomization untill date of any documented change in the serum concentration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine	serum creatinine concentration in mg/dl	up to 30 weeks from date of randomization untill date of any documented change in the serum concentration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of participants with signs of rejection	Fever , falnk pain , anuria	up to 30 weeks from date of randomization untill date of any documented rejectionoccurence of

Collaborators and Investigators

• Sponsor: Future University in Egypt
• Collaborators: Ain Shams University; Nasser Institute For Research and Treatment
• Investigators: Principal Investigator: Doaa MS ElBohy, M.Sc, Future university in egypt

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2016
• Primary Completion (Actual): December 10, 2016
• Study Completion (Actual): December 30, 2016

Study Registration Dates

• First Submitted: January 12, 2019
• First Submitted That Met QC Criteria: January 19, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Actual): January 24, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: kidney transplantation; Allograft rejection; cyclosporine; proton pump inhibitors; gastric complications.
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole; Pantoprazole
• Other Study ID Numbers: 7-2015/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No