Keeping RAASi Treatment With Optimal Potassium Control

NCT06578533 | Recruiting Phase 3

• 1 other identifier: KEEP-ON
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 5

Brief Summary

Phase III, multicenter, randomized, open-label, parallel-group, non-inferiority, phase III clinical trial comparing CSZ (Lokelma) vs. iSRAA discontinuation/reduction and/or ARM (standard treatment).

Conditions

Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Percentage of patients achieving serum potassium < 5.5mEq/L at three or all timepoints (7, 30, 60 or 90 days) after follow up (90 days) in both groups.

  To analyze the proportion of patients achieving sK of \< 5.5 mEq/L with Sodium zirconium cyclosilicate (SZC) versus discontinuation of RAASi and/or MRA in patients with hyperkalemia and non dialysis CKD.

  Through study completion, an average of 1 year

Secondary Outcomes (5)

• Percentage of patients achieving serum potassium < 5 mEq/L at two of the four temporal points in both groups.

  Through study completion, an average of 1 year

• Number of patients treated with SZC with reduction of serum potassium > 20% after baseline in each time point.

  Through study completion, an average of 1 year

• Percentage of patients achieving serum potassium below 5, 5.5, 6, 6.5 mEq/L in each time point.

  Through study completion, an average of 1 year

• Percentage of patients requiring additional treatments for hyperkalemia in both groups (potassium binding resins, adding or increasing loop diuretics, or discontinuation of RAASi and/or MRA in Lokelma group.

  Through study completion, an average of 1 year

• Mean change in the urine albumin-to-creatinine ratio (UACR) at 90 days from baseline in patients treated with SZC compared to RAASi / MRA discontinuation or downtitration.

  Through study completion, an average of 1 year

Other Outcomes (4)

• Mean and standard deviation comparation scores between groups at baseline and at the end of the study (visit 1 and 7) (MLHFQ and SF-36)

  Through study completion, an average of 1 year

• Proportion of patients in each group with downtitration (decrease 25 %, 50 % 75 % or discontinuation of RAASi or MRI) during the study.

  Through study completion, an average of 1 year

• Difference between mean hydration percentage with respect to baseline (OH/ECV *100) measured by multifrequency bioimpedance (BCM, Fresenius) at 90 days.

  Through study completion, an average of 1 year

Study Arms (2)

Control group

NO INTERVENTION

Patients assigned to this group will have their iSRAA and/or ARM treatment withdrawn or reduced, according to standard clinical practice.

Experimental group

EXPERIMENTAL

Patients assigned to this group will be maintained on treatment with iSRAA and/or ARM and oral treatment with CSZ (Lokelma) will be added. A single dose of CSZ consists of one to three sachets (5 to 10 g of active ingredient per sachet) that the subject must suspend in 45 mL of water.

Drug: Sodium Zirconium Cyclosilicate

Interventions

Sodium Zirconium Cyclosilicate DRUG

The recommended starting dose of Lokelma is 10 g, administered three times a day. If, at any time during the study, sK is \> 6.5 mEq/L, treatment for acute hyperkalemia will be started following common clinical practice and local protocols, and investigator will consider RAASi / MRA withdrawal, or downtitration. In this case (confirmed sK \> 6.5 mEq/L despite the maximum SZC dose) patient will leave the IP and will be counted as a treatment failure. If sK is ≤ 3.0 mEq/L, discontinue SZC. The subject should immediately receive appropriate medical intervention. If sK is between 3.1-5.1 mEq/L, pause SZC and re-evaluate in a week. This one-week SCZ treatment temporary discontinuation can only be applied once; if a new sK value between 3.1-5.1 mEq/L is detected, patient will leave the IP permanently. Depending on the serum potassium levels at each visit, the dose of SZC will be adjusted.

Also known as: Lokelma

Experimental group

Eligibility Criteria

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

You may qualify if:

• Patients must present serum potassium levels of 5.5-6.5 mEq/L at patient selection visit (V0)
• Patients must present serum potassium levels of 5.0-6.5 mEq/L at randomization visit (V1).
• Provision of patient or legal representative informed consent prior to any study specific procedures.
• Individuals receiving background standard of care for HF and treated according to locally recognized guidelines. Specific treatment should include RAASi and/or MRA treatment at first consultation and at least should have been stable for ≥ 4 weeks at maximum tolerated doses.
• Patients with CKD not on dialysis (Stages 2-5: estimated glomerular filtration rate (eGFR) between 15-60 ml/min/1,73m2 or eGFR between 60-90 ml/min/ 1.73 m2 with albuminuria/creatinuria (\> 30 mg/g) in the previous three months). The estimated GFR can be reported by the laboratory or calculated by the researcher with serum creatinine, age, and sex (CKD-EPI equation).
• years at the time of signing ICF.
• Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
• Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of SZC. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
• Previous enrollment or randomization in the present study.
• HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.
• Current acute decompensated HF, hospitalization due to decompensated HF, myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrollment.
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting or valvular repair/replacement within 12 weeks prior to enrollment or planned to undergo any of these operations after randomization).
• Implantation of a Cardiac Resynchronization Therapy (CRT) device or Implantable Cardioverter Defibrillator (ICD) within 12 weeks prior to enrollment or intent to perform atrial fibrillation ablation or to implant a CRT or ICD device.
• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or transplantation or implantation expected after randomization
• Oropharingeal dysfunction that precludes normal swallow.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Patients with amputated limbs or pacemaker devices will be excluded of bioimpedance analysis.
• Participation in another clinical study with an investigational product during the last 6 months.
• Patients with a known hypersensitivity to SZC or any of the excipients of the product.
• Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or the cation exchange polymer, patiromer sorbitex calcium (Veltassa®), within 7 days prior to the first dose of study drug.
• Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
• Subjects with a family history of long QT syndrome, presence of cardiac arrhythmias or conduction defects that require immediate treatment, or a QTc (corrected QT interval) of ≥ 550 msec.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (5)

Hospital General Universitario Dr. Balmis

Alicante, 03010, Spain

RECRUITING

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jose Luis Górriz

CONTACT

+34 96 197 38 11; jlgorriz@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III multicenter, randomized, open-label, parallel-group non-inferiority trial

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 29, 2024
• Study Start: September 30, 2022
• Primary Completion: July 30, 2025
• Study Completion (Estimated): July 30, 2026
• Last Updated: August 29, 2024

Record last verified: 2024-08

Locations

ES (5)