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Trial registered on ANZCTR


Registration number
ACTRN12621001626853
Ethics application status
Approved
Date submitted
23/09/2021
Date registered
29/11/2021
Date last updated
25/01/2024
Date data sharing statement initially provided
29/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II, prospective, open-label, dual-centre, single-arm feasibility study of Pregabalin for the management of uraemic pruritus in patients with End Stage Kidney Disease (ESKD) who are conservatively managed.
Scientific title
A Phase II, prospective, open-label, dual-centre, single-arm feasibility study of Pregabalin for the management of uraemic pruritus in patients with End Stage Kidney Disease (ESKD) who are conservatively managed.
Secondary ID [1] 304207 0
034/19
Universal Trial Number (UTN)
Trial acronym
Up Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uraemic pruritis 321898 0
End Stage Kidney Disease (ESKD) 321899 0
Condition category
Condition code
Renal and Urogenital 319626 319626 0 0
Kidney disease
Skin 321563 321563 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be asked to take oral pregabalin 25mg tablet every second evening for 4 weeks, followed by oral pregabalin tablet 50mg every second evening for 4 weeks, and then oral pregabalin tablet 75 mg every second evening for 4 weeks. This is the primary endpoint. After this, participants will take a gradually decreasing dose of oral pregabalin over 14 days reducing by 25mg every second day for seven days, then a further 25mg for seven days, at which point the dose will be zero. Participant adherence to the medication will be via verbal confirmation during telephone calls in week 2, 6 and 10, and inspection of the medication numbers and returns during the visits during weeks 4, 8 and 12 and at cessation.
Intervention code [1] 320542 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327486 0
To determine the feasibility of participant study recruitment (enrolment of a total of 24 participants over a 12 month period at 2 sites and retention rate of at least 60%). Measured via record of screening and recruitment data.
Timepoint [1] 327486 0
At 12 months after commencement of the study recruitment.
Secondary outcome [1] 395300 0
To compare participant rate of attrition using record of recruitment and retention
Timepoint [1] 395300 0
Record of participant withdrawal by weeks 4 and 12 post enrollment
Secondary outcome [2] 395301 0
To determine composite participant acceptability and burden of the study procedures via an informal exit interview with record of responses made into study record.
Timepoint [2] 395301 0
At 12 weeks after commencing treatment
Secondary outcome [3] 395303 0
To determine reason(s) for participant withdrawal with a semi-structured one to one exit interview (10 minutes) with those participants who agree.
Timepoint [3] 395303 0
At 12 weeks after commencing treatment or at time of withdrawal if prior to 12 weeks
Secondary outcome [4] 395304 0
To collect preliminary efficacy data relating to change in itch intensity using the WI-NRS
Timepoint [4] 395304 0
At 12 weeks compared to baseline.
Secondary outcome [5] 395305 0
To collect preliminary efficacy data relating to change in itch intensity by Pregabalin using the Integrated Palliative Care Outcome Scale (IPOS Renal)
Timepoint [5] 395305 0
At 2, 4, 8 and 12 weeks compared to baseline.
Secondary outcome [6] 395306 0
To assess composite patient experience of itch and quality of life using 5D-Itch scale
Timepoint [6] 395306 0
At 12 weeks compared to baseline
Secondary outcome [7] 395307 0
To assess a composite change in restless legs and pain using the IPOS-Renal Patient Version
Timepoint [7] 395307 0
At 12 weeks compared to baseline.
Secondary outcome [8] 395309 0
To assess the incidence of all adverse events, including AEs (Adverse events) and SAEs (Serious Adverse events) and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE V5).
Timepoint [8] 395309 0
At baseline and up to 14 weeks after commencing treatment (weeks 2, 4, 6, 8 and 10 and at exit (or Week 12) and 2 weeks of follow-up)
Secondary outcome [9] 395310 0
To assess changes in suicide risk over the 12 weeks using the Montgomery-Ashberg Depression Scale (MADRS)
Timepoint [9] 395310 0
At baseline and up to 14 weeks after commencing treatment (weeks 2, 4, 6, 8 and 10 and at exit (or Week 12) and 2 weeks of follow-up)
Secondary outcome [10] 395312 0
To assess patient symptom burden over the 12 week interventional period compared to baseline with a semi-structured one to one exit interview (10 minutes) with those participants who agree
Timepoint [10] 395312 0
At 12 weeks after commencing treatment or at time of withdrawal if prior to 12 weeks
Secondary outcome [11] 395313 0
To assess Carer’s experience using the Needs Assessment Tool for Caregivers (NAT-C)
Timepoint [11] 395313 0
At baseline and at 12 weeks after commencement of treatment or exit

Eligibility
Key inclusion criteria
18 years of age or more.
CKD 5 (eGFR<15) or CKD 4 (eGFR 15 -30)
Moderate to severe uraemic pruritus (WI-NRS=3) and chronic itch (> 6 weeks)
Able to read study questionnaires (5th grade level) in English.
Able to provide fully informed written consent
Capable of completing assessments, study diary and complying with the study procedures
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Itch not related to uraemic pruritus (as determined by a clinician). i.e. itch related to dermatological conditions, liver failure or cholestatic pruritus, neurological (post-herpetic neuralgia) and psychogenic disease.
Suicidality item in MADRS score >4
Known allergy or previous intolerance to Gabapentinoids (Pregabalin and Gabapentin).
Use of Gabapentinoids within the last 2 weeks.
High phosphate (PO4>2.5), corrected calcium (Ca2+>2.7) and low haemoglobin (Hb <80), Serum Iron (Fe2+>4)
Anuria
Clinician predicted survival less than one month
Pregnant or breastfeeding
Chronic alcoholism or drug abuse
Australian-modified Karnofsky performance score (AKPS) less than 50 at the beginning of the study
Participated in a clinical study of a new chemical entity within the month prior to study randomization

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
To address feasibility, recruitment and retention rates will be calculated.
The data collected from the itch diary will be presented using summary statistics (means and standard deviations, or medians and interquartile ranges depending on whether the data appeared to be normally distributed) and any differences between the arms will be calculated.
Analysis will be by intention to treat.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/05/2023
Actual
25/10/2023
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
24
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19428 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 19429 0
St George Hospital - Kogarah
Recruitment hospital [3] 24679 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 34009 0
2170 - Liverpool
Recruitment postcode(s) [2] 34010 0
2217 - Kogarah
Recruitment postcode(s) [3] 40299 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 308579 0
University
Name [1] 308579 0
University of Technology Sydney
Country [1] 308579 0
Australia
Primary sponsor type
University
Name
University of Technology Sydney
Address
IMPACCT, University of Technology Sydney
235 Jones Street Ultimo NSW 2007 Australia
Country
Australia
Secondary sponsor category [1] 309437 0
None
Name [1] 309437 0
Address [1] 309437 0
Country [1] 309437 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308520 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 308520 0
South Western Sydney Local Health District
Liverpool Hospital Eastern Campus
Scrivener Street
LIVERPOOL NSW 2170
Ethics committee country [1] 308520 0
Australia
Date submitted for ethics approval [1] 308520 0
31/05/2021
Approval date [1] 308520 0
30/07/2021
Ethics approval number [1] 308520 0
2021/ETH01101

Summary
Brief summary
Itch is a common and disabling symptom for people living with advanced kidney disease (termed Uraemic Pruritus (UP)). It causes skin irritation and bleeding, disrupts sleep, is associated with mood changes (depression) and often indicates a shortened survival. As many as 75% of patients, who are not receiving dialysis, suffer from UP. The cause of UP currently remains poorly understood.
Pregabalin is a medication which acts by desensitizing peripheral nerve fibers, which leads to a reduction of the itch sensation. It is an emerging drug that is becoming more commonly used in clinical practice to treat UP. However, current evidence is weak, and further research is required to definitely confirm the benefit of this medication.
This proposed Phase 2 Feasibility Study is an open-label, single arm, dose up-titration study that is looking at Pregabalin efficacy and tolerability in treating patients with moderate to severe UP who are being conservatively treated for End Stage Renal Failure (ESRF) (eGFR<30, CKD 4 and 5). The primary outcome measure is to recruit at least 24 patients over a 12 month period at both Liverpool and St George Hospitals. It is a 12 week study with the primary outcome measure at Week 4 which specifically looks at a Retention rate of >60. It is important to note that both hospitals contain large culturally and linguistically diverse (CALD) populations.
The results of this Phase 2 study will be used to design a subsequent Phase 3 study that will specifically look at the effectiveness of Pregabalin for the treatment of UP and may facilitate access to the medication through subsidised means, if found to be effective.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110994 0
Dr Rajesh Aggarwal
Address 110994 0
Bankstown-Lidcombe Hospital
Eldridge Rd, Bankstown NSW 2200
Country 110994 0
Australia
Phone 110994 0
+61 02 9722 8683
Fax 110994 0
Email 110994 0
[email protected]
Contact person for public queries
Name 110995 0
Rajesh Aggarwal
Address 110995 0
Bankstown-Lidcombe Hospital / Palliative Care & Renal Medicine
Eldridge Rd, Bankstown NSW 2200
Country 110995 0
Australia
Phone 110995 0
+61 02 9722 8683
Fax 110995 0
Email 110995 0
[email protected]
Contact person for scientific queries
Name 110996 0
Rajesh Aggarwal
Address 110996 0
Bankstown-Lidcombe Hospital / Palliative Care & Renal Medicine
Eldridge Rd, Bankstown NSW 2200
Country 110996 0
Australia
Phone 110996 0
+61 02 9722 8683
Fax 110996 0
Email 110996 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is feasibility data only and will not be sufficient for any other analysis


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.