Chronic Kidney DiseasesPhase 3KEEP-ONNCT06578533
Keeping RAASi Treatment With Optimal Potassium Control
A Phase 3 study testing Sodium Zirconium Cyclosilicate in people with Chronic Kidney Diseases, run by Fundación para la Investigación del Hospital Clínico de Valencia at 5 sites in Spain.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Diseases
- What is being tested?
- Sodium Zirconium Cyclosilicate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 5 sitesSpain
- Study dates
- 30 Sep 2022to 30 Jul 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- 18 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.
Who cannot join
- 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.
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- 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.
- History of QT prolongation associated with other medications that required discontinuation of that medications.
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Spain5 sites, 5 recruiting
- Recruiting
Hospital General Universitario Dr. Balmis
Alicante, 03010
Miriam Sandin
- Recruiting
Hospital Universitario Vall d'Hebrón
Barcelona, 08035
María José Soler Romeo, mjsoler01@gmail.com
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Juan Delgado Jiménez, juan.delgado@salud.madrid.org
- Recruiting
Hospital Clínico Universitario de Valencia
Valencia, 46010
Jose Luis Górriz, +34 96 197 38 11, jlgorriz@gmail.com
- Recruiting
Hospital Universitario Doctor Peset
Valencia, 46017
Jonay Pantoja Pérez, jonay.nefro@gmail.com
About this study
Official title: Phase III, Multicenter, Open-label, Randomized Clinical Trial to Evaluate Efficacy of Sodium Zirconium Cyclosilicate (Lokelma) Compared to Standard of Care to Manage Hyperkalemia in Patients With Chronic Kidney Disease (CKD)
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).
Read the detailed description
Hyperkalemia is a potentially life-threatening condition associated with ventricular arrhythmias and sudden cardiac arrest. It is common in patients with some comorbidities such as chronic kidney disease, congestive heart failure, cardiovascular disease, diabetes or liver disease. Most of these patients should receive drugs that block the renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRA), that increase the risk of hyperkalemia.
For these reasons, relatively few patients receive maximum doses of RAASi / MRA. The dose and its usage decline following an hyperkalemia episode. However, RAASi / MRA discontinuation because of hyperkalemia, represents an undesirable clinical scenario, loosing their potential cardiorenal and nephroprotective benefit. Patients on submaximum doses or who discontinued RAASi / MRA have worse outcomes than patients on maximum doses.
In this study 78 adult patients will be randomized to one of two treatment arms to analyze the proportion of patients achieving sK of < 5.5 mEq/L:
- Control group: they will have their treatment with iSRAA and/or ARM withdrawn or tapered, according to standard clinical practice.
- Experimental group: treatment with iSRAA and/or ARM will be maintained and oral treatment with CSZ (Lokelma) will be added.
The study will be conducted in 3 periods:
- Patient selection (Visit 0).
- Randomization (Visit 1).
- Follow up (Visits 2-7).
All the patients randomized and completing the treatment assigned will be participating in the study for an stimated period of 90 ± 13 d. The clinical trial will be finalized when the last 90-day follow-up of the last patient included is performed.
- Conditions
- Chronic Kidney Diseases
- Being tested
- Sodium Zirconium Cyclosilicate
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium Zirconium CyclosilicateDrug
Also called Lokelma
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Sodium Zirconium Cyclosilicate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
To determine if the percentage of patients achieving serum potassium < 5 mEq/L at two of the four temporal points is not inferior in SZC compared to RAASi / MRA discontinuation or downtitration.
Measured: 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.
To determine the number of patients treated with SZC who effectively reduce serum potassium > 20 % over the baseline at days 7, 30, 60 and 90 compared to RAASi / MRA discontinuation or downtitration.
Measured: 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.
To compare percentage of patients achieving serum potassium below 5, 5.5, 6, 6.5 mEq/L at days 7, 30, 60 and 90 in both groups.
Measured: 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.
To compare the need for additional treatments for serum hyperkalemia between both groups during the study (potassium binding resins, adding or increasing loop diuretics if hypervolemia).
Measured: 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.
To compare albuminuria changes at 90 days from baseline.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2024
- Study start30 Sep 2022
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase III multicenter, randomized, open-label, parallel-group non-inferiority trial
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de Valencia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06578533
- Sponsor's protocol ID
- KEEP-ON
- Acronym
- KEEP-ON
- Status last verified
- Sep 2025
- First submitted
- 26 Aug 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III, Multicenter, Open-label, Randomized Clinical Trial to Evaluate Efficacy of Sodium Zirconium Cyclosilicate (Lokelma) Compared to Standard of Care to Manage Hyperkalemia in Patients With Chronic Kidney Disease (CKD)
- ClinicalTrials.gov ID
- NCT06578533
- Acronym / sponsor ID
- KEEP-ON / KEEP-ON
- Conditions
- Chronic Kidney Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de ValenciaUniversity, hospital or other
- Study start
- 30 Sep 2022 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 29 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Hyperkalemia is a potentially life-threatening condition associated with ventricular arrhythmias and sudden cardiac arrest. It is common in patients with some comorbidities such as chronic kidney disease, congestive heart failure, cardiovascular disease, diabetes or liver disease. Most of these patients should receive drugs that block the renin angiotensin aldosterone system (RAASi) and mineralocorticoid receptor antagonists (MRA), that increase the risk of hyperkalemia.
For these reasons, relatively few patients receive maximum doses of RAASi / MRA. The dose and its usage decline following an hyperkalemia episode. However, RAASi / MRA discontinuation because of hyperkalemia, represents an undesirable clinical scenario, loosing their potential cardiorenal and nephroprotective benefit. Patients on submaximum doses or who discontinued RAASi / MRA have worse outcomes than patients on maximum doses.
In this study 78 adult patients will be randomized to one of two treatment arms to analyze the proportion of patients achieving sK of < 5.5 mEq/L:
- Control group: they will have their treatment with iSRAA and/or ARM withdrawn or tapered, according to standard clinical practice.
- Experimental group: treatment with iSRAA and/or ARM will be maintained and oral treatment with CSZ (Lokelma) will be added.
The study will be conducted in 3 periods:
- Patient selection (Visit 0).
- Randomization (Visit 1).
- Follow up (Visits 2-7).
All the patients randomized and completing the treatment assigned will be participating in the study for an stimated period of 90 ± 13 d. The clinical trial will be finalized when the last 90-day follow-up of the last patient included is performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase III multicenter, randomized, open-label, parallel-group non-inferiority trial
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Sodium Zirconium CyclosilicatePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Zirconium CyclosilicateAlso: LokelmaThe 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. | Drug | Experimental group |
Primary outcome
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.
Time frame: Through study completion, an average of 1 year
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.
5 secondary outcomes
Percentage of patients achieving serum potassium < 5 mEq/L at two of the four temporal points in both groups.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sodium Zirconium Cyclosilicate in people with Chronic Kidney Diseases, run by Fundación para la Investigación del Hospital Clínico de Valencia at 5 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jose Luis Górriz (+34 96 197 38 11, jlgorriz@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.