The ORTIZ Study: Optimising RASi Therapy With SZC

NCT04983979 | Terminated Phase 2 Results DMC

• 1 other identifier: 136721
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

CKD; Diabetes Mellitus, Type 2; Hyperkalemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Study end (week 12)

Secondary Outcomes (7)

• Change in Potassium From Baseline at Each Time Point

  At each study visit (weeks 1, 2, 4, 6, 8,12)

• Change in the BP at the End of the Study From Baseline

  Study end (week 12)

• Proportion of Patients Who Have a Potassium of >6mmol/l, or >6.5mmol/l at Any Time During the Study

  Cumulative across study follow-up, assessed at study end (week 12)

• Proportion of Patients Who Have a Potassium of <3.5mmol/l •

  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 •

  Cumulative. Calculated at each study visit. Assessed at study end (week 12).

Study Arms (2)

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

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

Drug: Placebo

Interventions

Sodium Zirconium Cyclosilicate DRUG

sachets of 5g or 10g given OD titrated to serum potassium

Also known as: Lokelma

SZC

Placebo DRUG

matched placebo given titrated according to potassium at a dose to 5 or 10g

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

Kieran Mccafferty

London, Uk, E1 1BB, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperkalemia

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Water-Electrolyte Imbalance

Limitations and Caveats

Early termination due to unacceptably slow rate of recruitment. 9 participants were randomised. Extensive statistical analysis would not be proportionate, would not have meaningful statistical power, and would not be amendable to the drawing of inferences in respect of trial hypotheses.

Results Point of Contact

• Title: Emily Kirkpatrick
• Organization: Queen Mary University of London

cvctu@qmul.ac.uk

02078825673

Study Officials

• Keiran McCafferty

  Barts & The London NHS Trust

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind randomised clinical trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Multi site, placebo controlled, double blind randomised clinical trial.

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 30, 2021
• Study Start: June 17, 2022
• Primary Completion: March 16, 2023
• Study Completion: May 16, 2023
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)