CKDPhase 2ORTIZNCT04983979
The ORTIZ Study: Optimising RASi Therapy With SZC
A Phase 2 study testing Sodium Zirconium Cyclosilicate in people with CKD and Diabetes Mellitus, Type 2, run by Barts & The London NHS Trust at 1 site in United Kingdom.
Trial summary
The hypothesis is that 3 months' treatment with SZC versus placebo will enable RASi (Irbesartan) maximisation in a cohort of patients with diabetic kidney disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CKD, Diabetes Mellitus, Type 2, Hyperkalemia
- What is being tested?
- Sodium Zirconium Cyclosilicate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Jun 2022to 16 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Able and willing to provide written informed consent
- Adults ≥ 18years old
- Type 2 Diabetes
- CKD defined as eGFR 25-60ml/min
- Albuminuria with uACR measured at >33.9.mg/mmol (300mg/g)
- On a stable (>4 weeks) of sub-maximal RASi dose, defined as any ACE or ARB dose up to and including 50% of maximum dose with evidence of hyperkalaemia potassium level >5.0mmol/l OR not currently on RASi therapy due to documented issues of hyperkalaemia in the past necessitating RASi discontinuation
Who cannot join
- Active malignancy
- Patients who lack capacity to give informed consent
- GI disturbance/chronic diarrhoea/stoma
- Subjects with a life expectancy of less than 3 months.
- Women who are pregnant, lactating, planning to become pregnant or unwilling to use effective methods of contraception during the study.
- Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated including NYHA class III/IV.
Show all 17Show fewer
- History of acute eGFR fall with RASi therapy (>30% in eGFR on initiation of RASi therapy)
- Known hypersensitivity or previous anaphylaxis to SZC or Irbesartan
- Hypotension: BP <120/70mm/hg at screening despite no antihypertensive agent use
- Uncontrolled Blood pressure: BP >170/110 at screening
- Evidence of prolonged QT on ECG QTc(f)>550msec
- History of QT prolongation associated with other medications that required discontinuation of that medication
- Treatment with lithium, or dual blockade with ACEi and ARB or mineralocorticoid inhibitor
- History of congenital long QT syndrome
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- Current or recent (within 3 months) participation in a clinical trial involving an investigational medicinal product.
- Current treatment with a potassium binder medication
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi Site, Placebo Controlled, Double Blind Randomised Clinical Trial Evaluating the Effectiveness of Sodium Zirconium Cyclosilicate Versus Placebo to Enable Safe Optimisation of RASi Therapy in Patients With Diabetic Kidney Disease.
The hypothesis is that 3 months' treatment with SZC versus placebo will enable RASi (Irbesartan) maximisation in a cohort of patients with diabetic kidney disease.
Read the detailed description
Inhibiting the renin angiotensin (RAS) system has been the cornerstone of therapy for patients with proteinuric CKD for almost 2 decades, to slow the decline in renal function, delay the presence of dialysis and reduce cardiovascular events and death.
There is evidence in both the cardiac and renal literature that suggests that maximising the dose of RAS therapy leads to improved outcomes over smaller doses of RAS therapy.
Indeed, many of the studies on which we base our care use doses which are higher than what the majority of our patients are taking. Thus patients are being systemically undertreated by therapies which have been shown to have robust reno protection. With up to 80% of patients on RASi therapy are not on maximal RASi therapy , putting them at risk of a more rapid progression and poorer outcomes and increased healthcare costs.
An important reason for this is the presence or fear around hyperkalaemia. With reports of significantly increased rate of hyperkalaemia seen following increases in prescribing of RASi therapy. These concerns have lead NICE to recommend not starting patients on RASi therapy if their potassium is >5mmol/l, and KDOQI guidelines recommending consideration of stopping RASi therapy if serum potassium is >5.5mmol/l.
ACE inhibitors and angiotensin receptor blockers are thought to confer long term renal protection through reduction of proteinuria. The reduction in glomerular pressure is a major mechanism leading to a reduction in proteinuria, and hence renal protection, however as a consequence there will also an acute fall in eGFR. Therefore, when starting/up titrating ACEi/ARB it is expected that there will be an acute fall in eGFR, which is expected to be more than compensated for due to the subsequent long term renal protection. Indeed, current NICE guidelines do not suggest any alteration in management until the drop in eGFR is >25%.
There is a currently huge unmet need to optimise RASi therapy in those patients with hyperkalaemia.
There have been recent advances in novel therapeutics which can lower potassium in patients. One such agent is Sodium zirconium cyclosilicate (SZC).
SZC is a highly selective inorganic cation exchanger designed to entrap potassium in the intestine.
It has been shown to effective in lowering potassium in patients with heart failure, Diabetes, CKD and RASi therapy. With around a 1mmol/l fall in the serum potassium on those treated with SZC, compared to placebo.
In the 5-large clinical trials it appears efficacious, well tolerated and safe.
- Conditions
- CKD, Diabetes Mellitus, Type 2, Hyperkalemia
- Being tested
- Sodium Zirconium Cyclosilicate, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperkalemia
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
sachets of 5g or 10g given OD titrated to serum potassium
PlaceboDrug
matched placebo given titrated according to potassium at a dose to 5 or 10g
| Study group | Role | What they receive |
|---|---|---|
| SZC | Experimental | 3 month treatment using Sodium zirconium cyclocilicate. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits Receives: Drug: Sodium Zirconium Cyclosilicate |
| Placebo | Placebo comparator | 3 month treatment using matched placebo. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients on Maximum Dose (300mg) Irbesartan Therapy at 12 Weeks Compared to Placebo
Difference in proportion of patients on maximum dose (300mg) Irbesartan therapy at the end of 12 weeks compared to placebo. Proportion is calculated per arm as number of individuals on maximum dose Irbesatan therapy divided by the number of individuals in the study arm. The difference in proportion is calculated as experimental arm - placebo comparator arm.
Measured: Study end (week 12)
Secondary outcomes (7)
Change in Potassium From Baseline at Each Time Point
Difference in potassium from baseline at each study visit (weeks 1, 2, 4, 6, 8,12) calculated as a mean for each study visit.
Measured: At each study visit (weeks 1, 2, 4, 6, 8,12)
Change in the BP at the End of the Study From Baseline
Difference in systolic and diastolic BP from baseline to end of study follow-up (week 12) calculated as a mean for each study visit.
Measured: Study end (week 12)
Proportion of Patients Who Have a Potassium of >6mmol/l, or >6.5mmol/l at Any Time During the Study
Difference in proportion of patients who have a potassium of >6mmol/l,, or >6.5mmol/l at any time during the study. Proportion is calculated per arm as number of individuals with a maximum potassium across study follow-up of >6mmol/l or >6.5mmol/l divided by the number of individuals in the study arm. The difference in proportion is calculated as experimental arm - placebo comparator arm.
Measured: Cumulative across study follow-up, assessed at study end (week 12)
Proportion of Patients Who Have a Potassium of <3.5mmol/l •
Difference in proportion of patients who have a potassium of <3.5mmol/l at any time during the study. Proportion is calculated per arm as number of individuals with a minimum potassium of <3.5mmol/l across study follow-up divided by the number of individuals in the study arm. The difference in proportion is calculated as experimental arm - placebo comparator arm.
Measured: Cumulative across study follow-up, assessed at study end (week 12)
Proportion of Patients Whose Glomerular Filtration Rate (GFR) Falls by >30% From the Previous Visit •
Difference in proportion of patients with a sudden drop in GFR defined as >30% decreased between study visits. Proportion is calculated per arm as number of individuals experiencing a sudden drop of GFR divided by the number of individuals in the study arm. The difference in proportion is calculated as experimental arm - placebo comparator arm.
Measured: Cumulative. Calculated at each study visit. Assessed at study end (week 12).
Change in GFR at the End of Study From Baseline
Difference in GFR from baseline to end of study follow-up (week 12) calculated as a mean for each study visit.
Measured: Study end (week 12)
Frequency of Adverse Events
A count of the number of adverse events reported in each study arm
Measured: Study end (week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2021
- Study start17 Jun 2022
- Primary completion16 Mar 2023
- Study completion16 May 2023
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CKDStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A Multi site, placebo controlled, double blind randomised clinical trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Keiran McCafferty, Study chair, Barts & The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04983979
- Sponsor's protocol ID
- 136721
- Acronym
- ORTIZ
- Status last verified
- Jun 2025
- First submitted
- 9 Jul 2021
- Last updated
- 8 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi Site, Placebo Controlled, Double Blind Randomised Clinical Trial Evaluating the Effectiveness of Sodium Zirconium Cyclosilicate Versus Placebo to Enable Safe Optimisation of RASi Therapy in Patients With Diabetic Kidney Disease.
- ClinicalTrials.gov ID
- NCT04983979
- Acronym / sponsor ID
- ORTIZ / 136721
- Conditions
- CKD, Diabetes Mellitus, Type 2, Hyperkalemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Study start
- 17 Jun 2022 (actual)
- Primary completion
- 16 Mar 2023 (actual)
- Study completion
- 16 May 2023 (actual)
- First posted
- 30 Jul 2021 (actual)
- Results
- Posted 8 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis is that 3 months' treatment with SZC versus placebo will enable RASi (Irbesartan) maximisation in a cohort of patients with diabetic kidney disease.
Detailed description
Inhibiting the renin angiotensin (RAS) system has been the cornerstone of therapy for patients with proteinuric CKD for almost 2 decades, to slow the decline in renal function, delay the presence of dialysis and reduce cardiovascular events and death.
There is evidence in both the cardiac and renal literature that suggests that maximising the dose of RAS therapy leads to improved outcomes over smaller doses of RAS therapy.
Indeed, many of the studies on which we base our care use doses which are higher than what the majority of our patients are taking. Thus patients are being systemically undertreated by therapies which have been shown to have robust reno protection. With up to 80% of patients on RASi therapy are not on maximal RASi therapy , putting them at risk of a more rapid progression and poorer outcomes and increased healthcare costs.
An important reason for this is the presence or fear around hyperkalaemia. With reports of significantly increased rate of hyperkalaemia seen following increases in prescribing of RASi therapy. These concerns have lead NICE to recommend not starting patients on RASi therapy if their potassium is >5mmol/l, and KDOQI guidelines recommending consideration of stopping RASi therapy if serum potassium is >5.5mmol/l.
ACE inhibitors and angiotensin receptor blockers are thought to confer long term renal protection through reduction of proteinuria. The reduction in glomerular pressure is a major mechanism leading to a reduction in proteinuria, and hence renal protection, however as a consequence there will also an acute fall in eGFR. Therefore, when starting/up titrating ACEi/ARB it is expected that there will be an acute fall in eGFR, which is expected to be more than compensated for due to the subsequent long term renal protection. Indeed, current NICE guidelines do not suggest any alteration in management until the drop in eGFR is >25%.
There is a currently huge unmet need to optimise RASi therapy in those patients with hyperkalaemia.
There have been recent advances in novel therapeutics which can lower potassium in patients. One such agent is Sodium zirconium cyclosilicate (SZC).
SZC is a highly selective inorganic cation exchanger designed to entrap potassium in the intestine.
It has been shown to effective in lowering potassium in patients with heart failure, Diabetes, CKD and RASi therapy. With around a 1mmol/l fall in the serum potassium on those treated with SZC, compared to placebo.
In the 5-large clinical trials it appears efficacious, well tolerated and safe.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A Multi site, placebo controlled, double blind randomised clinical trial.
| Arm | Type | Receives |
|---|---|---|
| SZC | Experimental | Drug: Sodium Zirconium Cyclosilicate3 month treatment using Sodium zirconium cyclocilicate. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits |
| Placebo | Placebo comparator | Drug: Placebo3 month treatment using matched placebo. Doses of 5 or 10g once daily will be used. The dose will be titrated according to potassium levels performed at clinic visits |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Able and willing to provide written informed consent
- Adults ≥ 18years old
- Type 2 Diabetes
- CKD defined as eGFR 25-60ml/min
- Albuminuria with uACR measured at >33.9.mg/mmol (300mg/g)
Key exclusion criteria (17 listed)
- Active malignancy
- Patients who lack capacity to give informed consent
- GI disturbance/chronic diarrhoea/stoma
- Subjects with a life expectancy of less than 3 months.
- Women who are pregnant, lactating, planning to become pregnant or unwilling to use effective methods of contraception during the study.
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: Lokelmasachets of 5g or 10g given OD titrated to serum potassium | Drug | SZC |
| Placebomatched placebo given titrated according to potassium at a dose to 5 or 10g | Drug | Placebo |
Primary outcome
Proportion of Patients on Maximum Dose (300mg) Irbesartan Therapy at 12 Weeks Compared to Placebo
Time frame: Study end (week 12)
Difference in proportion of patients on maximum dose (300mg) Irbesartan therapy at the end of 12 weeks compared to placebo. Proportion is calculated per arm as number of individuals on maximum dose Irbesatan therapy divided by the number of individuals in the study arm. The difference in proportion is calculated as experimental arm - placebo comparator arm.
7 secondary outcomes
Change in Potassium From Baseline at Each Time Point
Time frame: At each study visit (weeks 1, 2, 4, 6, 8,12)
Change in the BP at the End of the Study From Baseline
Time frame: Study end (week 12)
Proportion of Patients Who Have a Potassium of >6mmol/l, or >6.5mmol/l at Any Time During the Study
Time frame: Cumulative across study follow-up, assessed at study end (week 12)
Proportion of Patients Who Have a Potassium of <3.5mmol/l •
Time frame: Cumulative across study follow-up, assessed at study end (week 12)
Proportion of Patients Whose Glomerular Filtration Rate (GFR) Falls by >30% From the Previous Visit •
Time frame: Cumulative. Calculated at each study visit. Assessed at study end (week 12).
Change in GFR at the End of Study From Baseline
Time frame: Study end (week 12)
Frequency of Adverse Events
Time frame: Study end (week 12)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Keiran McCafferty study chair
Barts & The London NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium Zirconium Cyclosilicate in people with CKD and Diabetes Mellitus, Type 2, run by Barts & The London NHS Trust at 1 site in United Kingdom.
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 6 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: stopped early, as of the sponsor's last update on 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients on Maximum Dose (300mg) Irbesartan Therapy at 12 Weeks Compared to Placebo (time frame: Study end (week 12)). 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 8 Jun 2025.