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CTRI Number  CTRI/2023/04/051363 [Registered on: 06/04/2023] Trial Registered Prospectively
Last Modified On: 17/04/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   A study to evaluate Sodium Zirconium Cyclosilicate on Chronic Kidney Disease Progression 
Scientific Title of Study   A Phase 3, International, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Effect of Sodium Zirconium Cyclosilicate on Chronic Kidney Disease (CKD) Progression in Participants with CKD and Hyperkalaemia or at Risk of Hyperkalaemia (STABILIZE CKD) 
Trial Acronym  STABILIZE-CKD 
Secondary IDs if Any  
Secondary ID  Identifier 
D9488C00001, Version 2.0, (Amendment 1) dated 08 Jun 2022  Protocol Number 
NCT05056727  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)  
Name  Dr. Dinesh Khullar 
Designation  Chairman - Nephrology & Renal Transplant Medicine 
Affiliation  Max Super Speciality Hospital (A unit of Max Healthcare Institute Limited) 
Address  1, Press enclave Road, Saket, New Delhi

New Delhi
DELHI
110017
India 
Phone  9810124066  
Fax    
Email  Dinesh.Khullar@maxhealthcare.com  
 
Details of Contact Person
Scientific Query  
Name  Mr Tapankumar Shah 
Designation  Senior Director, Asia Area Cluster Head, Site Management & Monitoring 
Affiliation  AstraZeneca Pharma India Ltd. 
Address  Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road Bangalore

Bangalore
KARNATAKA
560045
India 
Phone  9535104975  
Fax    
Email  Tapankumar.Shah@astrazeneca.com  
 
Details of Contact Person
Public Query  
Name  Mr Tapankumar Shah 
Designation  Senior Director, Asia Area Cluster Head, Site Management & Monitoring 
Affiliation  AstraZeneca Pharma India Ltd. 
Address  Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road Bangalore


KARNATAKA
560045
India 
Phone  9535104975  
Fax    
Email  Tapankumar.Shah@astrazeneca.com  
 
Source of Monetary or Material Support  
AstraZeneca AB 151 85 Sodertalje, Sweden 
 
Primary Sponsor  
Name  AstraZeneca Pharma India Ltd. 
Address  Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045,Karnataka 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
AstraZeneca AB  151 85 Södertälje Sweden 
 
Countries of Recruitment     Argentina
Brazil
Bulgaria
Canada
China
India
Italy
Japan
Malaysia
Mexico
Philippines
Poland
Russian Federation
Spain
Taiwan
Thailand
Turkey
Ukraine
United States of America
Viet Nam  
Sites of Study
Modification(s)  
No of Sites = 11  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Arunkumar Subbiah  All India Institute of Medical Sciences, New Delhi  Ansari Nagar, New Delhi – 110029
New Delhi
DELHI 		 9968969076

gmedaks@gmail.com 
Dr Atanu Pal  IPGME&R and SSKM Hospital  Department of Nephrology, No. 244, AJC Bose Road, Kolkata, West Bengal – 700020, India
Kolkata
WEST BENGAL 		 9433121697

dratanup@gmail.com 
Dr Kamal Goplani  K D Hospital  Department of Nephrology, Vaishnavdevi Circle, S.G.Highway, Ahmedabad Gujarat – 382421
Ahmadabad
GUJARAT 		 9512016866

kamalgoplani@gmail.com 
Dr Ramaswami Sethuraman  KG Hospital and Post Graduate Medical Institute & Research Centre  Department of Nephrology, No. 5, Government Arts College Road, Coimbatore, Tamil Nadu - 641018, India
Coimbatore
TAMIL NADU 		 9600900078

ramaswami.sethuraman@gmail.com 
Dr Ritesh Vernekar  KLES Dr Prabhakar Kore Hospital & Medical Research Centre  Nehru Nagar Belagavi, PIN 590010
Belgaum
KARNATAKA 		 9449061633

riteshvernekar@gmail.com 
Dr Dinesh Khullar  Max Super Speciality Hospital  Department of Nephrology, 1, Press enclave Road, Saket, New Delhi – 110017
New Delhi
DELHI 		 9810124066

Dinesh.Khullar@maxhealthcare.com 
Dr Sampathkumar Krishnaswamy  Meenakshi Mission Hospital & Research Centre  Department of Nephrology, Lake Area, Melur Road, Madurai, Tamil Nadu – 625107
Madurai
TAMIL NADU 		 9994872250

drksampath@gmail.com 
Dr Abhijit Madhav Konnur  Muljibhai Patel Urological Hospital  Department of Nephrology, Dr. Virendra Desai Road, Nadiad, Gujarat – 387001
Kheda
GUJARAT 		 9825316112

abhijit@mpuh.org 
Dr Raja Ramachandran  Post Graduate Institute of Medical Education & Research (PGIMER)  Department of Nephrology, Chandigarh, Sector 12, Punjab – 160012
Chandigarh
CHANDIGARH 		 9216958874

drraja1980@gmail.com 
Dr Krishna MVS  Sunrise Hospital  Department of Nephrology, Opp. Corporation Bank, Bellapu Sobhanandri Road, Vijayawada Andhra Pradesh – 520002
Krishna
ANDHRA PRADESH 		 9848148967

drsaikrishnamaddi@gmail.com 
Dr Anupam Agarwal  VMMC and Safdarjung Hospital  Department of Nephrology, Ansari Nagar, New Delhi – 110029
New Delhi
DELHI 		 9968667606

anupamagarwal08@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 11  
Name of Committee  Approval Status 
Institute Ethics Committe All India Institute of Medical Sciences  Approved 
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centre  Approved 
Institutional Ethics Committee KG Hospital  Approved 
Institutional Ethics Committee KLE  Approved 
Institutional Ethics Committee PGIMER  Approved 
Institutional Ethics Committee Sunrise Hospital  Approved 
Institutional Ethics Committee VMMC and SJH  Approved 
IPGMEandR Research Oversight Committee  Approved 
KD Hospital Institutional Ethics Committee  Approved 
Max Healthcare Ethics Committee  Approved 
MPSRNUEC Muljibhai Patel Urological Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: E875||Hyperkalemia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Sodium Zirconium Cyclosilicate  10 g Sodium Zirconium Cyclosilicate TID for up to 72 hours until normokalaemic or 5 g Sodium Zirconium Cyclosilicate QD for 48 hours, depending of serum potassium level (Initiation Phase). 5 g Sodium Zirconium Cyclosilicate QOD or 5, 10, or 15 g QD (Run-in Phase). 5 g Sodium Zirconium Cyclosilicate or placebo administered QOD or 5, 10, or 15 g Sodium Zirconium Cyclosilicate or placebo administered QD (Maintenance phase). 
Comparator Agent  Sodium Zirconium Cyclosilicate matching placebo  10 g Sodium Zirconium Cyclosilicate TID for up to 72 hours until normokalaemic or 5 g Sodium Zirconium Cyclosilicate Placebo QD for 48 hours, depending of serum potassium level (Initiation Phase). 5 g Sodium Zirconium Cyclosilicate QOD or 5, 10, or 15 g QD (Run-in Phase). 5 g Sodium Zirconium Cyclosilicate or placebo administered QOD or 5, 10, or 15 g Sodium Zirconium Cyclosilicate or placebo administered QD (Maintenance phase) 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  90.00 Year(s)
Gender  Both 
Details  1 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
2 Must be more than or equal to 18 years of age at the time of signing the informed consent
3 Must have eGFR more than or equal to 25 and less than or equal to 59 mLmin1.73m2 as calculated by central laboratory CKDEPI formula at screening Visit 1
4 Must have UACR more than or equal to 200 and less than or equal to 5000 mg per g as calculated by central laboratory at screening Visit 1 If the first sample does not fulfil eligibility criteria a second sample can be obtained during the screening period if so the UACR measurement from the second
sample must be within the eligibility range
5 Any of the following criteria a or b at screening Visit 1
a Cohort A Hyperkalaemia SK more than 5 to less than or equal to 6 point 5 mmol per L as measured by the central laboratory and on adequate or limited RAASi therapy due to hyperkalaemia.
b Cohort B Normokalaemia SK more than or equal to 3 point 5 to less than or equal to 5 mmol per L as measured by the central laboratory and on limited RAASi therapy due to high risk of hyperkalaemia High risk of hyperkalaemia is defined as
i Participants with a previous medical history or record of hyperkalaemia within the prior 24 months who are on limited RAASi therapy despite indication in CKD
ii Participants in whom RAASi therapy is indicated in CKD who are on limited RAASi therapy and have SK more than or equal to 4 point 7 to less than or equal to 5 mmol per L
iii Participants in whom RAASi therapy has been discontinued or reduced to suboptimal doses because of hyperkalaemia
Adequate RAASi dose levels doses lower than these are considered as suboptimal
Limited RAASi therapy is defined as no or suboptimal RAASi therapy according to dosing guidance provided
6 If on thiazide or loop diuretics, the dose must have been stable for 2 weeks prior to screening Visit 1.
7 If on RAASi therapy, the dose must have been stable for one month prior to screening Visit 1 and remain stable during screening
8 If on an SGLT2 inhibitor ie dapagliflozin and canagliflozin finerenone or any other medications in these 2 classes that are approved for CKD the dose must have been stable for 3 months prior to screening Visit 1
Contraceptive use by participants of childbearing potential should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
9 Participants must be one-year postmenopausal surgically sterile or using one highly effective form of birth control defined as one that can achieve a failure rate of less than 1 percentage per year when used consistently and correctly They should have been stable on their chosen method of birth control for a minimum of one month prior to screening Visit 1 and willing to remain on the birth control until one month after the last dose of study intervention 
 
ExclusionCriteria 
Details  1 New York Heart Association class III to IV congestive heart failure at the time of screening Visit 1 or previous history of severe or symptomatic heart failure
2 Myocardial infarction unstable angina stroke or transient ischaemic attack within 3 months prior to screening Visit 1
3 Participants with a known history of systolic blood pressure more than or equal to 160 mmHg or diastolic blood pressure more than or equal to 95 mmHg within 2 weeks prior to screening Visit 1 are excluded In addition any participant with systolic blood pressure more than or equal to 160 mmHg or diastolic blood pressure more than or equal to 95 mmHg as measured at screening Visit 1 and confirmed by repeated
measurement is excluded Participants may be rescreened once blood pressure is controlled
4 QTcF more than 550 msec at screening Visit 1
5 History of QT prolongation associated with other medications that required discontinuation of that medication
6 Congenital long QT syndrome
7 Symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia Participants with atrial fibrillation and heart rate controlled by medication are permitted
9 Lupus nephritis or anti-neutrophil cytoplasmic antibody associated vasculitis
10 Change in renal function requiring hospitalisation or dialysis within 3 months prior to screening Visit 1
11 History of renal transplant or anticipated need for renal transplant during the study
12 Severe hepatic impairment biliary cirrhosis or cholestasis
13 History of hereditary or idiopathic angioedema
14 Any prior hypersensitivity to ACEi or ARB that in the investigator’s judgment precludes use of lisinopril and valsartan/irbesartan Prior hypersensitivity reactions to consider include but are not limited to development of angioedema icterus hepatitis or neutropaenia or thrombocytopaenia requiring treatment modification
15 Known hypersensitivity or previous anaphylaxis to SZC or to components thereof
16 Any condition outside the CV and renal disease area such as but not limited to malignancy with a life expectancy of less than 2 years based on investigators clinical judgment
17 Active malignancy requiring treatment at the time of screening Visit 1 except for successfully treated basal cell or treated squamous cell carcinoma
18 SK more than 6 point 5 or less than 3 point 5 mmol per L by local laboratory within 1 day prior to the scheduled first dose of SZC in the initiation phase
19 Evidence of COVID-19 infection within 2 weeks prior to screening Visit 1
20 Treated with dual blockade of RAAS combined use of an ACEi and ARB within 3 months prior to screening Visit 1
21 Treated with an angiotensin receptor neprilysin inhibitor ARNI sacubitril or valsartan within 3 months prior to screening Visit 1
22 Treated with an MRA not approved for CKD within 3 months prior to screening Visit 1
23 Treated with aliskiren containing products with 3 months prior to screening Visit 1
24 Treated with SPS CPS patiromer or SZC within 7 days prior to screening Visit 1
25 Participation in another clinical study with an investigational product administered within one month prior to screening Visit 1
26 Not willing or not able to change to lisinopril or valsartan or irbesartan the protocol mandated RAASi study intervention Note For participants taking a fixed combination of an ACEi or ARB with another agent eg calcium blockers or diuretics as
SoC the investigator must make a judgment that it will be safe and efficacious for such participants to change to the study ACEi or ARB and to the other drug as separate agents
27 Previous dosing with SZC in the present study
28 Currently pregnant confirmed with positive pregnancy test at screening Visit 1 or breastfeeding
29 Judgment by the investigator that the participant is unlikely to comply with study procedures restrictions and requirements
30 Involvement in the planning and or or conduct of the study applies to both AstraZeneca staff and/or staff at the study site 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
To determine if treatment with SZC as adjunct to ACEi/ARB therapy (lisinopril or valsartan) is superior to placebo in slowing CKD progression, assessed as the reduction in participant’s expected eGFR decline over time  Co-primary
Total slope- eGFR measurements starting at randomisation
Chronic slope- eGFR measurements, starting at 12 weeks after randomisation 
 
Secondary Outcome  
Outcome  TimePoints 
To determine if treatment with SZC, as adjunct to ACEi/ARB therapy (lisinopril or valsartan a), is superior to placebo in reducing the incidence of the composite of kidney failure outcomes comprising: sustained ≥ 40% decline in eGFR, onset of ESKD, and death from kidney failure  Time from randomisation to the first occurrence 
To determine if treatment with SZC, as adjunct to ACEi/ARB therapy (lisinopril or valsartan a), is superior to placebo in reducing the incidence of lisinopril/valsartan dose decrease, in participants on lisinopril/valsartan at randomisation  Time from randomisation to first dose decrease 
To determine if treatment with SZC, as adjunct to ACEi/ARB therapy (lisinopril or valsartan a), is superior to placebo in reducing albuminuria  At scheduled visits after randomisation 
To determine if treatment with SZC, as adjunct to ACEi/ARB therapy (lisinopril or valsartan a), is superior to placebo in increasing serum bicarbonate levels  At scheduled visits after randomization 
To determine if treatment with SZC, as adjunct to ACEi/ARB therapy (lisinopril or valsartan a), is superior to placebo on maintenance of normokalaemia  At scheduled visits after randomisation 
 
Target Sample Size   Total Sample Size="1360"
Sample Size from India="60" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   08/05/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  30/09/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="4"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Suspended 
Recruitment Status of Trial (India)  Suspended 
Publication Details   none yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This is a Phase 3, international, randomised withdrawal, double-blind, parallel-group, placebo-controlled study, to evaluate the effect of SZC as adjunct to RAASi therapy (lisinopril or valsartan) in slowing CKD progression in participants with CKD and hyperkalaemia or at risk of hyperkalaemia.

 

Specifically, the study will include participants with hyperkalaemia (S-K > 5.0 to ≤ 6.5 mmol/L by central laboratory) who are on adequate or limited RAASi therapy due to hyperkalaemia, and participants with normokalaemia (S-K ≥ 3.5 to ≤ 5.0 mmol/L by central laboratory) who are on limited RAASi therapy due to high risk of hyperkalaemia. High risk of hyperkalaemia is defined as (1) participants with a previous medical history or record of hyperkalaemia within the prior 24 months who are on limited RAASi therapy despite indication in CKD; (2) participants in whom RAASi therapy is indicated in CKD but are on limited RAASi therapy and have S-K ≥ 4.7 to ≤ 5.0 mmol/L; and (3) participants in whom RAASi therapy has been discontinued or reduced to suboptimal doses because of hyperkalaemia.

 

A participant is expected to be in the study for approximately 28 months, which includes up to 13 days for the screening period, 27 months for the intervention period, and 1 week for follow-up. The 27-month intervention period of the study consists of 3 phases, an initiation phase (up to 72 hours), a run-in phase (3 months/up to Day 90), and a maintenance phase (24 months/104 weeks).

 

The initial dose of SZC will be administered to participants during the initiation phase. No changes will be made to the ACEi or ARB therapy at this stage. As soon as possible after the participant is confirmed to be normokalaemic at the end of the initiation phase, the participant will enter the run-in phase. Participants will receive open-label SZC and either lisinopril or valsartan. The aim of the run-in phase is to increase ACEi or ARB therapy stepwise to their maximum doses. After a 3-month run-in period for RAASi dose optimization while on SZC, participants will be randomized to SZC or placebo and followed during the subsequent 24 months of maintenance phase for efficacy and safety assessments.
 
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