Effects of Patiromer on Pharmacokinetics of Immunosuppresive Drugs in Renal Transplant Recipients (TACPAT)

Patiromer lowers potassium effectively in patients with hyperkalemia and chronic kidney disease. Patients with a kidney transplant usually have reduced renal function and may also develop hyperkalemia. However, potential interactions between immunosuppressive medications and patiromer have not been evaluated. These interactions could involve change in AUC of immunosuppressive drugs, such as calcineurin inhibitors or mycophenolate, or increased risk of hypomagnesemia, since both tacrolimus and patiromer have this potential side effect. We wish to evaluate potential interactions to ensure safe use of this drug in the transplant population.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia; Kidney Transplant
• Intervention / Treatment: Drug: Patiromer Oral Product

Detailed Description

Patients with a kidney transplant may develop hyperkalemia. This could be due to different mechanisms. In some patients it could be due to reduced kidney function. In others, it could be secondary to renal tubular acidosis type 4 caused by necessary medications used after transplantation.

The most important medicines contributing to hyperkalemia after kidney transplantation are calcineurin inhibitors which are a compulsory part of the immunosuppressive regimen, ACE inhibitors or ARBs in patients with hypertension, and trimethoprim-sulfa, which is used as infection prophylaxis in all patients during the first 6 months after transplantation. In the weeks after renal transplantation around 5-10% of transplant patients at our institution at some point develop hyperkalemia above the limit where some type of management of hyperkalemia would be indicated. As the drugs mentioned above can rarely or not at all be withdrawn after transplantation, most doctors will either observe the hyperkalemia untreated or try to lower the potassium level.

In outpatients with s-potassium of 5 - 6.5, urgent management is usually not necessary. However, some kind of intervention is still indicated, to make sure that the potassium will decrease during the next days. Patiromer could be an interesting alternative in those kidney transplanted patients that are in this category. We are not aware of any published studies describing the use of patiromer in the transplant population. We intend to investigate if there is any pharmacokinetic interaction between patiromer and immunosuppressive drugs affecting the blood concentration of the latter.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0024
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Renal transplant recipients, at least 3 weeks after transplantation, who receive Tacrolimus as part of their immunosuppressive therapy, with stabile tacrolimus dose and trough tacrolimus concentration.
2. Recipients 18 years of age or older.
3. Hyperkalemia (K>5 and <6,0)
4. Signed informed consent.

Exclusion Criteria:

1. Concomitant treatment with: diltiazem, verapamil, fenytoin, carbamazapin, fluconazole, ketoconazole, vorikonazole, erythromycin, clarithromycin, resonium-calcium, and/or sodium zirconium cyclosilicate.
2. Constipation, defined as fewer than three bowel movements per week.
3. Hypomagnesemia less than 0.6 mmol/L.
4. Serum potassium level of greater than 6.0 mEq/L.
5. Increased immunologic risk patient (DSA, ABO-incompatible transplant).
6. Pregnancy or suspected pregnancy (pregnancy is excluded at time of transplantation by measuring HCG, kidney transplanted patients should not become pregnant before at least one year after transplant, and no transplanted patient has ever become pregnant during the first weeks after transplantation. They are all informed regarding different types of contraception). Fertile women will be tested for pregnancy before inclusion.
7. Hypersensitivity/allergy to patiromer.
8. Other serious medical or psychiatric condition likely to interfere with participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All patients use both patiromer and tacrolimus; Pharmacokinetic investigation of tacrolimus performed in both the presence and absence of patiromer for all patients.	Drug: Patiromer Oral Product; interaction study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
study potential interaction between patiromer and tacrolimus	Log-transformed AUC0-tau of tacrolimus between patiromer vs. no patiromer	two weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine effect of patiromer on potassium concentration.	Delta-value change of serum potassium from start of treatment to 7 days after start of treatment, and delta-value change of serum potassium from 7 days after start of treatment to 7 days after end of treatment.	two weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: kidney transplant; Hyperkalemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: 148684

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: no plan

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