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Trial registered on ANZCTR


Registration number
ACTRN12617000599370
Ethics application status
Approved
Date submitted
18/04/2017
Date registered
27/04/2017
Date last updated
17/12/2021
Date data sharing statement initially provided
17/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of oral nicotinamide (vitamin B3) on skin cancer incidence and actinic keratoses in kidney, liver, heart and lung transplant recipients: a randomised controlled Phase 3 trial
Scientific title
EFFECT OF ORAL NICOTINAMIDE ON NON-MELANOMA SKIN CANCER INCIDENCE AND ACTINIC KERATOSES IN RENAL, HEPATIC, HEART AND LUNG TRANSPLANT RECIPIENTS: A RANDOMISED CONTROLLED TRIAL
Secondary ID [1] 291644 0
Nil known
Universal Trial Number (UTN)
U1111-1195-2309
Trial acronym
ONTRANS: Oral Nicotinamide after TRANSplant
Linked study record

Health condition
Health condition(s) or problem(s) studied:
non-melanoma skin cancer 302786 0
basal cell carcinoma 302787 0
cutaneous squamous cell carcinoma 302788 0
actinic keratoses 302789 0
Condition category
Condition code
Cancer 302290 302290 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral nicotinamide 500mg or placebo twice daily for 12 months. Adherence to intervention monitored by drug tablet return.
Intervention code [1] 297724 0
Prevention
Intervention code [2] 297725 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet containing calcium hydrogen phosphate anhydrous and cellulose microcrystalline. Taken orally twice daily for 12 months
Control group
Placebo

Outcomes
Primary outcome [1] 301698 0
Number of nonmelanoma skin cancers (basal cell carcinomas + cutaenous squamous cell carcinomas + squamous cell carcinomas in situ + keratoacanthomas) assessed by histological examination of lesions detected during dermatological followup.
Timepoint [1] 301698 0
Over the 12 months from randomisation
Secondary outcome [1] 333588 0
Numbers of actinic keratoses assessed by clinical counting
Timepoint [1] 333588 0
Over the 6 months from randomisation
Secondary outcome [2] 333589 0
Numbers of nonmelanoma skin cancers confirmed by histology
Timepoint [2] 333589 0
During each of the four 3-monthly intervals from baseline to 12 months post randomisation
Secondary outcome [3] 333590 0
Numbers of basal cell carcinomas confirmed by histology
Timepoint [3] 333590 0
Over the 12 months from randomisation
Secondary outcome [4] 333591 0
Numbers of cutaneous squamous cell carcinomas (including squamous cell carcinomas in situ and keratoacanthomas) confirmed by histology
Timepoint [4] 333591 0
Over the 12 months from randomisation
Secondary outcome [5] 333592 0
Skin cancer recurrences, occurring at sites of previously histologically confirmed skin cancer, assessed by histology
Timepoint [5] 333592 0
Over the 12 months from randomisation
Secondary outcome [6] 333593 0
Skin tumour markers of skin cancer proliferation, immune cell infiltration and DNA damage assessed with immunohistochemistry. SCC differentiation and BCC subytype assessed by histology
Timepoint [6] 333593 0
On skin cancers developing at any timepoint over the 12 months from randomisation
Secondary outcome [7] 333594 0
Change in self-reported quality of life assessed by:
-Skin Cancer Index
-Short Form 36
Timepoint [7] 333594 0
At 12 months after randomisation
Secondary outcome [8] 333783 0
Safety profile of oral nicotinamide on patient and graft outcomes in transplant recipients, assessed by serum creatinine and eGFR, full blood count, electrolytes, liver function tests; urinary protein
Timepoint [8] 333783 0
At 1, 3, 6, 9 and 12 months after randomisation

Eligibility
Key inclusion criteria
1. Prior renal, hapatic, heart or lung transplant performed more than 12 months ago
2. At least two histologically confirmed nonmelanoma skin cancers within the past 5 years
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unstable renal or liver function
2. Acute rejection within the past 3 months
3. Immune suppression due to noniatrogenic causes (eg haematological malignancy, HIV)
4. Severe liver function abnormality (transaminases >3x normal; bilirubin >1.5x normal)
5. Active peptic ulcer disease
6. Myocardial infarction within the past 6 months
7. Hypotension (systolic BP < 90 mmHg)
8. Renal impairment with eGFR < 20 mL/min/1.73 m2
9. Internal malignancy, metastatic SCC or invasive melanoma or Merkel cell carcinoma within the past five years
10. Need for ongoing carbamazepine use (possible interaction with nicotinamide)
11. Patient unavailable for follow-up for the duration of the study because of general frailty, geographical, social or other reasons
12. Gorlin’s syndrome or other genetic skin cancer syndrome
13. Large areas of confluent skin cancer (> 20 cm diameter) at baseline preventing accurate assessment and counting of new skin cancers
14. Pregnancy or lactation
15. Patients commencing acitretin or other oral retinoids within the past 6 months (patients taking acitretin for six months or longer are eligible for randomisation)
16. Patients commencing mTor inhibitors within the past 6 months (patients taking mTor inhibitors for six months or longer are eligible for randomisation)
17. Supplemental nicotinamide or niacin (as part of a multivitamin preparation) at doses greater than 20mg daily within the past 4 weeks.
18. Taking pharmacological doses of nicotinamide (equal to or greater than 500mg daily) (nicotinamide to be ceased 3 months prior to study commencement).
19. Field treatment for actinic keratoses (AKs; topical use of 5 fluorouracil, imiquimod, diclofenac, retinoids; topical photodynamic therapy for AKs; laser resurfacing or chemical peel treatments for AKs) within the previous 4 weeks. Field treatments for AKs are permitted in the second half of the intervention period (ie after the 6 month visit) if considered medically necessary.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All eligible patients enrolled on the study will be entered into the central randomisation system. The patient number assigned at the time of randomisation will be the primary identifier for the patient. Randomisation will be performed by the NHMRC Clinical Trials Centre which will provide a centralised tele-randomisation service that will randomly allocate patients to nicotinamide or placebo groups in a 1:1 ratio stratified by baseline skin cancer count, gender, transplant group (renal, liver, heart, lung), current retinoid and/or mTor inhibitor use and study site. The pharmacist will provide the drug kit allocated by the system for the patient, recording the kit number in the pharmacy log. The study number, patient name and MRN will then be written on the medication bottle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised to nicotinamide or placebo in a 1:1 ratio using a minimisation method stratified by baseline skin cancer count, (6 or more versus 2-5 previous nonmelanoma skin cancers), gender, study site, transplant group (renal, liver, heart, lung), current oral retinoid use and current mTor inhibitor use.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/05/2017
Actual
16/05/2017
Date of last participant enrolment
Anticipated
31/12/2018
Actual
29/08/2019
Date of last data collection
Anticipated
31/12/2019
Actual
30/09/2020
Sample size
Target
254
Accrual to date
Final
158
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 7804 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 7805 0
Westmead Hospital - Westmead
Recruitment hospital [3] 7806 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 7807 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [5] 7808 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 10525 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [7] 21359 0
Sunshine Coast University Hospital - Birtinya
Recruitment postcode(s) [1] 15737 0
2050 - Camperdown
Recruitment postcode(s) [2] 15738 0
2145 - Westmead
Recruitment postcode(s) [3] 15739 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 15740 0
3050 - Parkville
Recruitment postcode(s) [5] 15741 0
5000 - Adelaide
Recruitment postcode(s) [6] 15788 0
3053 - Carlton
Recruitment postcode(s) [7] 22240 0
2065 - St Leonards
Recruitment postcode(s) [8] 36251 0
4575 - Birtinya

Funding & Sponsors
Funding source category [1] 296137 0
Government body
Name [1] 296137 0
National Health and Medical Research Council
Country [1] 296137 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Sydney Medical School
University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 295034 0
None
Name [1] 295034 0
Address [1] 295034 0
Country [1] 295034 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297389 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 297389 0
Ethics committee country [1] 297389 0
Australia
Date submitted for ethics approval [1] 297389 0
Approval date [1] 297389 0
26/05/2016
Ethics approval number [1] 297389 0
HREC/16/RPAH/98

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73894 0
Prof Diona Damian
Address 73894 0
Dermatology, University of Sydney
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 73894 0
Australia
Phone 73894 0
+61 2 9515 8295
Fax 73894 0
+61 2 9565 1048
Email 73894 0
diona.damian@health.nsw.gov.au
Contact person for public queries
Name 73895 0
Diona Damian
Address 73895 0
Dermatology, University of Sydney
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 73895 0
Australia
Phone 73895 0
+61 2 9515 8295
Fax 73895 0
+61 2 9565 1048
Email 73895 0
diona.damian@health.nsw.gov.au
Contact person for scientific queries
Name 73896 0
Diona Damian
Address 73896 0
Dermatology, University of Sydney
Gloucester House Level 3
Royal Prince Alfred Hospital
Missenden Rd
Camperdown NSW 2050
Country 73896 0
Australia
Phone 73896 0
+61 2 9515 8295
Fax 73896 0
+61 2 9565 1048
Email 73896 0
diona.damian@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
Dimensions AIFeasibility of a trial to evaluate nicotinamide for chemoprevention of skin cancers in organ transplant recipients in the UK2020https://doi.org/10.1111/bjd.18982
EmbaseNicotinamide for skin cancer chemoprevention in transplant recipients.2023https://dx.doi.org/10.1111/ajd.14045
EmbaseNicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.2023https://dx.doi.org/10.1056/NEJMoa2203086
N.B. These documents automatically identified may not have been verified by the study sponsor.