A Phase 2 interventional study of Sodium Zirconium Cyclosilicate and Placebo in CKD, Diabetes Mellitus, Type 2 and Hyperkalemia, sponsored by Barts & The London NHS Trust. Terminated at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-08.
Sponsored by Barts & The London NHS Trust · Phase 2, Interventional, and Treatment
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.
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.
10,371 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,406 are open to participants now.
This study's enrollment of 18 is below the median of 80 across 8,350 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →Barts & The London NHS Trust is the lead sponsor of 151 studies on the registry; 21 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: Sodium Zirconium Cyclosilicate
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
Drug: Placebo
sachets of 5g or 10g given OD titrated to serum potassium
Also known as: Lokelma
matched placebo given titrated according to potassium at a dose to 5 or 10g
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.
Time frame: Study end (week 12)
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.
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
Difference in systolic and diastolic BP from baseline to end of study follow-up (week 12) calculated as a mean for each study visit.
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
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.
Time frame: 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.
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 •
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.
Time frame: 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.
Time frame: Study end (week 12)
Frequency of Adverse Events
A count of the number of adverse events reported in each study arm
Time frame: Study end (week 12)
| Milestone | Experimental: SZC | Placebo Comparator: Placebo |
|---|---|---|
| Started | 4 | 5 |
| Completed | 4 | 5 |
| Not completed | 0 | 0 |
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.
| Participants | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| Number of participants reaching maximum dose of irbesartan | 2 | 3 |
| Number of participants with no available data on irbesartan dose | 1 | 0 |
| Number of participants who did not reach maximum dose of irbesartan | 1 | 2 |
Difference in potassium from baseline at each study visit (weeks 1, 2, 4, 6, 8,12) calculated as a mean for each study visit.
| mmol/L | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| Week 1 | -0.58 ± 0.53 | 0.06 ± 0.42 |
| Week 2 | -0.03 ± 0.45 | 0.24 ± 0.54 |
| Week 4 | 0.10 ± 0.23 | 0.08 ± 0.36 |
| Week 6 | -0.10 ± 0.54 | 0.16 ± 0.23 |
| Week 8 | 0.05 ± 0.52 | 0.16 ± 0.52 |
| Week 12 | -0.50 ± 0.50 | 0.16 ± 0.48 |
Difference in systolic and diastolic BP from baseline to end of study follow-up (week 12) calculated as a mean for each study visit.
| mmHg | Sodium Zirconium Cyclocilicate | Placebo |
|---|---|---|
| Systolic BP | -3.75 ± 26.80 | -28.90 ± 28.20 |
| Diastolic BP | 1.38 ± 10.54 | -7.40 ± 12.75 |
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.
| Participants | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| Proportion of Patients Who Have a Potassium of >6mmol/l, or >6.5mmol/l at Any Time During the Study | 1 | 0 |
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.
| Participants | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| Proportion of Patients Who Have a Potassium of <3.5mmol/l • | 0 | 0 |
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.
| Participants | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| Proportion of Patients Whose Glomerular Filtration Rate (GFR) Falls by >30% From the Previous Visit • | 1 | 0 |
Difference in GFR from baseline to end of study follow-up (week 12) calculated as a mean for each study visit.
| mL/min/1.73m^2 | Sodium Zirconium Cyclosilicate (SZC) | Placebo |
|---|---|---|
| eGFR at Baseline | 41.00 ± 18.49 | 42.80 ± 12.58 |
| eGFR at 12 weeks | 35.00 ± 16.19 | 40.80 ± 7.79 |
| Difference from baseline | -6.0 ± 2.83 | -2.00 ± 7.28 |
A count of the number of adverse events reported in each study arm
| adverse events across participants | Sodium Zirconium Cyclocilicate | Placebo |
|---|---|---|
| Frequency of Adverse Events | 6 | 6 |
Collected over 16 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Experimental: SZC | 0/4 (0%) | 0/4 (0%) | 3/4 (75%) |
| Placebo Comparator: Placebo | 0/5 (0%) | 1/5 (20%) | 2/5 (40%) |
| Event | Experimental: SZC | Placebo Comparator: Placebo |
|---|---|---|
| Broken left humerusSurgical and medical procedures | 0/4 | 1/5 |
| Event | Experimental: SZC | Placebo Comparator: Placebo |
|---|---|---|
| Stomach CrampsGastrointestinal disorders | 1/4 | 0/5 |
| BradycardiaCardiac disorders | 1/4 | 0/5 |
| HypoglycaemiaBlood and lymphatic system disorders | 1/4 | 1/5 |
| ItchinessSkin and subcutaneous tissue disorders | 1/4 | 0/5 |
| Shortness of breathRespiratory, thoracic and mediastinal disorders | 1/4 | 0/5 |
| OedemaBlood and lymphatic system disorders | 0/4 | 1/5 |
| ConstipationGastrointestinal disorders | 0/4 | 1/5 |
| Fluid overloadEndocrine disorders | 0/4 | 1/5 |
| Weight gainGeneral disorders | 0/4 | 1/5 |
| Worsening hypertensionCardiac disorders | 0/4 | 1/5 |
Total 9 participants
| Age, Categorical(Participants) | Sodium Zirconium Cyclosilicate (SZC) | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 2 | 5 |
| >=65 years | 1 | 3 | 4 |
| Age, Continuous(years) | Sodium Zirconium Cyclosilicate (SZC) | Placebo | Total |
|---|---|---|---|
| Mean | 57.5 ± 9.5 | 58.0 ± 14.2 | 57.8 ± 11.6 |
| Sex: Female, Male(Participants) | Sodium Zirconium Cyclosilicate (SZC) | Placebo | Total |
|---|---|---|---|
| Female | 0 | 1 | 1 |
| Male | 4 | 4 | 8 |
| Race/Ethnicity, Customized(Participants) | Sodium Zirconium Cyclosilicate (SZC) | Placebo | Total |
|---|---|---|---|
| Caucasian | 1 | 1 | 2 |
| Asian | 2 | 4 | 6 |
| Other | 1 | 0 | 1 |
| Type of Medical Histpry(participants) | Sodium Zirconium Cyclosilicate (SZC) | Placebo | Total |
|---|---|---|---|
| Diabetes | 3 | 5 | 8 |
| Hypertension | 1 | 3 | 4 |
| Kidney disease | 1 | 4 | 5 |
| Other | 2 | 2 | 4 |
| Unknown | 1 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
This study is terminated, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Sodium zirconium cyclosilicate
Barts & The London NHS Trust →