Patiromer Trial in CKD Stage IIIB to V

NCT05786469 | Terminated Phase 3

• 2 other identifiers: DROP2023-503984-41-00
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III, prospective, randomized, double-blind, placebo-controlled trial will primarily aim to compare the effects of patiromer and placebo on the rate of withdrawal or down-titration of RAAS inhibition therapy because of refractory hyperkalemia (serum K+ levels ≥ 5.5 mEq/L at two consecutive visits, one-week apart) in non-dialysis patients with CKD stage IIIB to V receiving best available conservative therapy, including RAAS inhibition with ACE inhibitors and/or ARBs and/or aldosterone antagonists. Patients are expected to be included during an 18-month recruitment period. All randomized patients will be maintained on active follow-up for 12 months. At 12 months, a final visit will be performed for all patients who complete the follow-up period. During this final visit, all the parameters evaluated at baseline will be reassessed and the study treatment will be discontinued. Whenever feasible, a final visit will be planned within one month also for those patients who prematurely discontinue the treatment period for any intercurrent reason (adverse event, consent withdrawal and other). After the final visit the patient will be discharged from the study and will be referred to his nephrologist with the suggestion to check serum potassium levels within three days.

Conditions

Hyperkalemia

Keywords

Chronic Kidney Diseases; Hyperkalemia; Potassium Binders

Outcome Measures

Primary Outcomes (1)

• To compare the effects of patiromer and placebo on the rate of withdrawal or down-titration of RAAS inhibition therapy because of refractory hyperkalemia

  Number of patients who withdraw or reduce RAAS inhibition therapy because of refractory hyperkalemia (serum K+ levels ≥ 5.5 mEq/L at two consecutive visits one-week apart)

  6 months

Secondary Outcomes (8)

• To compare changes in serum potassium normalization between the two treatment groups

  6 months

• To compare changes in metabolic laboratory parameters between the two treatment groups

  6 months

• To compare changes in renal function parameters between the two treatment groups

  6 months

• To compare change in clinical parameters between the two treatment groups

  6 months

• To compare events between the two treatment groups

  6 months

Study Arms (2)

Participants randomized to receive one 8.4 g packet of patiromer per day

EXPERIMENTAL

Patiromer is an organic, non-absorbed, sodium-free, potassium-binding polymer that exchanges potassium for calcium in the gastrointestinal tract.

Drug: Veltassa Oral Powder Product

Participants randomized to receive one identical packet containing placebo

PLACEBO COMPARATOR

Active study treatment and placebo will be provided by Vifor Pharma and will be indistinguishable from one another in terms of labelling and instructions

Other: Placebo

Interventions

Veltassa Oral Powder Product DRUG

The recommended starting dose is 8.4 g of patiromer, once daily (equivalent to one packet of the active ingredient, once daily). The daily dose may be adjusted in intervals of one week or longer, based on the serum potassium level and the desired target range. The daily dose may be increased or decreased by 8.4 g as necessary to reach the desired target range, up to a maximum dose of 25.2 g daily. If serum potassium falls below the desired range, the dose should be reduced or discontinued. Patients are expected to be included during an 18-month recruitment period. The last randomized patient will be maintained on active follow-up for 6 months. All other randomized patients will be maintained on active follow-up until the last randomized patient will have completed the planned 6-month follow-up period. Thus, the follow-up period will be expected to range from a minimum of 6 months for the last randomized patient to a maximum of 24 months for the first randomized patient

Participants randomized to receive one 8.4 g packet of patiromer per day

Placebo OTHER

The recommended starting dose is 8.4 g of patiromer, once daily (equivalent to one packet of the active ingredient, once daily). The daily dose may be adjusted in intervals of one week or longer, based on the serum potassium level and the desired target range. The daily dose may be increased or decreased by 8.4 g as necessary to reach the desired target range, up to a maximum dose of 25.2 g daily. If serum potassium falls below the desired range, the dose should be reduced or discontinued. Patients are expected to be included during an 18-month recruitment period. The last randomized patient will be maintained on active follow-up for 6 months. All other randomized patients will be maintained on active follow-up until the last randomized patient will have completed the planned 6-month follow-up period. Thus, the follow-up period will be expected to range from a minimum of 6 months for the last randomized patient to a maximum of 24 months for the first randomized patient

Participants randomized to receive one identical packet containing placebo

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study-specific procedures.
• Age \>18 years.
• GFR \<45 ml/min/1.73m2 as per CKD-EPI equation.
• Serum potassium ≥5.0 mEq/L (in at least two consecutive evaluations, one week apart) despite dietary counseling, optimized metabolic acidosis control, diuretic therapy as needed for blood pressure control and fluid balance, and effective blood glucose control in diabetics.
• Concomitant therapy with RAAS inhibitors (ACE inhibitors, ARBs and aldosterone antagonists, such as spironolactone and finerenone).

You may not qualify if:

• Ongoing treatment with SPS before randomization (Patient eligibility could be reassessed during the screening period after at least one week from SPS therapy withdrawal)
• Rapidly progressive kidney disease (eGFR reduction ≥ 30% over the last three months as per CKD-Epi equation) and expected risk of progression to ESKD and need of renal replacement therapy by dialysis or transplantation within six months.
• Active systemic autoimmune diseases.
• Concomitant treatment with steroids or any other immunosuppressive agent.
• Hypersensitivity to the active ingredient or any of the excipients. Patients with Hereditary Fructose Intolerance.
• Patients with or at risk of hypercalcaemia and/or hypomagnesaemia.
• Severe/unstable heart failure with or without decreased systolic function requiring hospitalization or changes in pharmacological therapy over the last three months.
• Refractory severe hypertension (BP \>180/100 mmHg despite optimized pharmacological treatment with at least three blood pressure-lowering medications and a diuretic).
• Positive hepatitis C antibodies, hepatitis B virus surface antigens at screening.
• Known to have tested positive for human immunodeficiency virus.
• Drug or alcohol abuse.
• Female subjects who are pregnant, lactating or who intend to become pregnant before or during the study period, or within 90 days of the last dose of study treatment. Female subjects who intend to donate ova over the same time period.
• Male subjects who intend to donate sperm during the study period or for the 90 days following the last dose of study treatment.
• Male and female subjects in childbearing age not using a highly effective contraception method according to the 2020 CTFG Recommendations related to contraception and pregnancy testing in clinical trials (9)
• Inability to fully understand the potential risks and benefits related to study participation.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Vifor Pharma: collaborator

Study Sites (1)

Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"

Ranica, BG, 24020, Italy

Location

MeSH Terms

Conditions

Hyperkalemia; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active study treatment and placebo will be provided by Vifor Pharma and will be indistinguishable from one another in terms of labelling and instructions. Allocation to one of the two treatments will be determined by the randomization's number based on a computer-generated randomization list developed by the Mario Negri Biostatistics Laboratory.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: DOUBLE-BLIND, RANDOMIZED, SINGLE CENTRE TRIAL

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 27, 2023
• Study Start: August 2, 2023
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)