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Trial registered on ANZCTR


Registration number
ACTRN12619001053112p
Ethics application status
Submitted, not yet approved
Date submitted
4/06/2019
Date registered
26/07/2019
Date last updated
26/07/2019
Date data sharing statement initially provided
26/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Red blood cell transfusion schedule in myelodysplastic syndromes: study 2 (REDDS-2)
Scientific title
A randomised feasibility n-of-1 trial of weekly-interval red cell transfusion myelodysplastic syndromes
Secondary ID [1] 297973 0
Nil known
Universal Trial Number (UTN)
U1111-1231-6575
Trial acronym
REDDS-2
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic syndromes (MDS) 312382 0
Condition category
Condition code
Cancer 311342 311342 0 0
Other cancer types
Blood 311688 311688 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Weekly red blood cell transfusion using matched red blood cells, for a total of 6 weeks.
Duration of each transfusion will be as per local institutional practice.
Due to the n-of-1 study design, the number of units per week will be individualised for each participant, based on averaging their pre-trial transfusion requirements. This will be determined for each patient individually and approved by their treating clinician and the study PI, prior to randomisation.
There will not be a wash-out period between treatments, as these patients are transfusion dependent hence there cannot be a no-transfusion period.
The transfusion will be administered by the research nurse or physician.

Intervention code [1] 314485 0
Treatment: Other
Comparator / control treatment
Usual transfusion schedule for each participant (ie the patient's current transfusion schedule). This will differ for each patient. In most cases, this will be typically 2-4 red cell units transfused every 2-6 weeks.

This comparator treatment differs from the intervention treatment which will consist of weekly red cell transfusion.
Control group
Active

Outcomes
Primary outcome [1] 320070 0
Feasibility of weekly transfusion. This will be assessed by the difference in time interval between transfusions for the two arms. The trial will be deemed feasible if the median difference in time between transfusion episodes is at least 7 days.

Data will be collected via study specific case report forms.
Timepoint [1] 320070 0
12 weeks post intervention commencement.
Secondary outcome [1] 370427 0
Number of RBC units transfused per arm.
Data will be collected via study specific case report forms.
Timepoint [1] 370427 0
Cumulative measurement over the entire trial treatment period.
Data will be collected via study specific case report forms at each study visit (day 0, weeks 3,6,9,12 post commencement of treatment).
Secondary outcome [2] 370428 0
Proportion of transfusions in the weekly arm provided with fully matched RBC units.
Data will be collected via study specific case report forms.
Timepoint [2] 370428 0
Cumulative measurement over the entire trial treatment period.
Data will be collected via study specific case report forms at each study visit (day 0, weeks 3,6,9,12 post commencement of treatment).
Secondary outcome [3] 370429 0
Proportion of Hb measures falling within the target range (to ensure the transfusion strategy maintains Hb levels in the target ranges).
Timepoint [3] 370429 0
Cumulative measurement over the entire trial treatment period.
Data will be collected via study specific case report forms at each study visit (day 0, weeks 3,6,9,12 post commencement of treatment).
Secondary outcome [4] 370430 0
Change in scores on the quality of life surveys: QUALMS-1, EQ-5D and EORTC-QLQc30.
Timepoint [4] 370430 0
Measured at:
1) baseline prior to commencement of treatment
2) the last transfusion visit during arm A (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
3) the last transfusion visit during arm B (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
Secondary outcome [5] 370431 0
Functional activity thresholds and measures (via 6-minute walk test).
Timepoint [5] 370431 0
Measured at:
1) baseline prior to commencement of treatment
2) the last transfusion visit during arm A (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
3) the last transfusion visit during arm B (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
Secondary outcome [6] 370432 0
Change in scores on the community integration questionnaire.
Timepoint [6] 370432 0
Measured at:
1) baseline prior to commencement of treatment
2) week 6 post commencement of treatment
3) week 12 post commencement of treatment
Secondary outcome [7] 370433 0
Numbers of adverse events per arm, including transfusion reactions, disease progression, via study specific case report forms.
Timepoint [7] 370433 0
Adverse events will be documented during study visits (week 3,6,9,12 post commencement of treatment), and a follow-up phone call and review of medical records at 3 months post study treatment conclusion.
Any unexpected SAEs (as per the study protocol) or expected SAE that ends in death must be notified by participating sites to the Principle Investigators and Monash TRU within 24 hours of the site identifying the event.
Secondary outcome [8] 370434 0
Number of patients developing new RBC alloantibodies, assessed by red cell serology studies.
Timepoint [8] 370434 0
Measured via a blood test taken:
1) at baseline
2) prior to each RBC transfusion episode
3) at each study visit (weeks 3,6,9,12)

Documentation of red cell serology results at 3 months follow-up post study treatment conclusion (based on routinely collected laboratory results) will also be done.
Secondary outcome [9] 370435 0
Enrolment rates including number of screening failures.
This will be assessed by use of a screening log at all sites.
Timepoint [9] 370435 0
Cumulative measurement over the entire trial treatment period.
Secondary outcome [10] 370438 0
Exploring patient experiences of the weekly transfusion strategy (qualitative study).
Timepoint [10] 370438 0
Patient interviews will be conducted during the last 2 weeks of the participant's trial treatment.
Secondary outcome [11] 370439 0
Time from patient admission to transfusion, as measured by the study staff and documented in the study specific case report form.
Timepoint [11] 370439 0
At each transfusion visit.
Secondary outcome [12] 370440 0
Percentage of patients and in Arm B receiving weekly transfusions.
Timepoint [12] 370440 0
Cumulative measurement over the entire trial treatment period.
This will be collected via case report forms during each transfusion visit (the exact time will vary per individual patient).
Secondary outcome [13] 370443 0
Pre-transfusion Hb levels, as measured by the Hb result from the Full Blood Count (blood test) taken pre-transfusion.
Timepoint [13] 370443 0
Measured prior to each transfusion.
Secondary outcome [14] 372643 0
Proportion of Hb measures falling below the target range (to ensure the transfusion strategy maintains Hb levels in the target ranges).
Timepoint [14] 372643 0
Data will be collected via study specific case report forms at each study visit (day 0, weeks 3,6,9,12)
Secondary outcome [15] 372644 0
Proportion of Hb measures falling above the target range (to ensure the transfusion strategy maintains Hb levels in the target ranges).
Timepoint [15] 372644 0
Data will be collected via study specific case report forms at each study visit (day 0, weeks 3,6,9,12)
Secondary outcome [16] 372645 0
Functional activity thresholds and measures, via handgrip strength as measured by dynanometer
Timepoint [16] 372645 0
Measured at:
1) baseline
2) the last transfusion visit during arm A (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
3) the last transfusion visit during arm B (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
Secondary outcome [17] 372646 0
Functional activity thresholds and measures (via accelerometer).
Timepoint [17] 372646 0
Measured at:
1) baseline
2) the last transfusion visit during arm A (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
3) the last transfusion visit during arm B (the exact timepoint will vary per individual participant, depending on their transfusion schedule)
Secondary outcome [18] 372647 0
Exploring staff experiences of the weekly transfusion strategy (qualitative study).
Timepoint [18] 372647 0
Staff focus groups will be conducted at the start (after the 3rd patient is enrolled at the site) and conclusion of the trial. If 3 or fewer patients are enrolled at the site, there will only be one focus group conducted at the end of the trial.
Secondary outcome [19] 372648 0
Percentage of transfusion episodes in arm B, which were given weekly.
Timepoint [19] 372648 0
Cumulative measurement over trial period.
Data will be collected via case report forms at each transfusion visit (the exact time may vary for each individual patient).
Secondary outcome [20] 372649 0
Percentage of patients in Arm B receiving apheresis single donor platelets.
This will be documented by study staff in the study specific case report forms.
Timepoint [20] 372649 0
Measured at each transfusion visit during Arm B.

Eligibility
Key inclusion criteria
.Patients aged 18 years and above with WHO-defined MDS or mixed myeloproliferative/myelodysplastic neoplasm overlap syndromes (MPN/MDS)
.Transfusion dependent: at least two transfusion episodes and at least four units of RBCs, in total during the 16 weeks prior to study entry
.Life expectancy 6 months or greater
.Continuing RBC transfusion requirement expected for at least 6 months
.No new treatments likely to affect transfusion requirements during the study period
.Able to complete quality of life and community integration questionnaires (CIQ)
.Able to complete tests of physical function (6-minute walk test, hand-grip strength, use of accelerometer).
.Red cell phenotyping and/or genotyping results available and reasonable certainty that matched RBCs can be provided for the duration of the study
.For the qualitative study, able to converse in conversational English for the purposes of the interviews
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
.Currently receiving RBC transfusion at an interval of less than or equal to 7 days
.Unable to tolerate a weekly transfusion schedule, as determined by the treating clinician
.Poor performance/functional status (Eastern Cooperative Oncology Group system ECOG greater than or equal to 3)
.Patients on erythropoietic-stimulating agent (ESA) or disease-modifying agents for their MDS (such as lenalidomide, azacitidine, hydroxycarbamide, experimental agents)
.Patients with myelofibrosis
.Patients presenting with active bleeding or evidence of significant haemolysis
.Splenomegaly greater than 5cm below the costal margin
.Patients with greater than 2 known RBC alloantibodies and/or patients with rare blood groups or RBC antigen types which complicate cross-matching

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
n-of-1 study design.
All participants will receive both arms of treatment, in a randomly allocated sequence. Both treatment arms will be individualised per patient.
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment outside Australia
Country [1] 21480 0
United Kingdom
State/province [1] 21480 0
Country [2] 21481 0
Netherlands
State/province [2] 21481 0

Funding & Sponsors
Funding source category [1] 302497 0
Charities/Societies/Foundations
Name [1] 302497 0
Australian & New Zealand Society of Blood Transfusion (ANZSBT)
Address [1] 302497 0
145 Macquarie Street, Sydney NSW 2000, Australia
Country [1] 302497 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Transfusion Research Unit
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Road
Melbourne
VIC 3004
Country
Australia
Secondary sponsor category [1] 302726 0
None
Name [1] 302726 0
Address [1] 302726 0
Country [1] 302726 0
Other collaborator category [1] 280704 0
Government body
Name [1] 280704 0
NHS Blood and Transplant
Address [1] 280704 0
Oak House Reeds Crescent, Watford WD24 4QN
Country [1] 280704 0
United Kingdom
Other collaborator category [2] 280855 0
Hospital
Name [2] 280855 0
Radboud University Medical Center
Address [2] 280855 0
Geert Grooteplein Zuid 10, 6525 GA Nijmegen, Netherlands
Country [2] 280855 0
Netherlands

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303153 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 303153 0
Research Support Services
Level 2, i Block,
Monash Medical Centre
246 Clayton Road
Clayton, Victoria 3168
Ethics committee country [1] 303153 0
Australia
Date submitted for ethics approval [1] 303153 0
01/05/2019
Approval date [1] 303153 0
Ethics approval number [1] 303153 0
Ethics committee name [2] 303431 0
North East – Newcastle and North Tyneside 1
Ethics committee address [2] 303431 0
NHSBT Newcastle Blood Donor Centre, Holland Dr, Newcastle upon Tyne NE2 4NQ
Ethics committee country [2] 303431 0
United Kingdom
Date submitted for ethics approval [2] 303431 0
01/08/2019
Approval date [2] 303431 0
Ethics approval number [2] 303431 0

Summary
Brief summary
This study aims to assess the feasibility of a low dose, weekly red blood cell (RBC) transfusion for haemoglobin stability in patients with Myelodysplastic syndromes (MDS).

Who is it for?

You may be eligible for this study if you are an adult with MDS or mixed myeloproliferative/myelodysplastic neoplasm overlap syndrome (MPN/MDS) and who is transfusion dependent (at least two transfusion episodes and at least four units of RBC, in the last 16 weeks)

Study details

All eligible participants will be randomly allocated to either the usual care Arm A, (continue with their standard treatment) or to the Intervention group, Arm B. The Arm B intervention will involve weekly RBC transfusion using phenotype/genotype matched red blood cells. The number of units per week will be individualised for each patient in the intervention group. All participants involved will experience both treatment arms during the study.

Participants will attend weekly transfusions for 6 weeks .The assessment will involve quality of life questionnaires and blood tests.

It is possible that maintaining a more stable haemoglobin between transfusions, by transfusing a smaller number of RBCs weekly, may improve quality of life of participants and reduce symptoms.

REDDS2 is a collaborative study with the UK National Health Service Blood and Transplant (UK NHSBT) and will inform the design and conduct of a larger trial that will compare red cell transfusion strategies in patients with transfusion-dependent MDS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92662 0
A/Prof Zoe McQuilten
Address 92662 0
Transfusion Research Unit
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Road
Melbourne, Victoria 3004
Country 92662 0
Australia
Phone 92662 0
+61 3 99030379
Fax 92662 0
Email 92662 0
zoe.mcquilten@monash.edu
Contact person for public queries
Name 92663 0
Dr Allison Mo
Address 92663 0
Transfusion Research Unit
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Road
Melbourne, Victoria 3004
Country 92663 0
Australia
Phone 92663 0
+61 399030055
Fax 92663 0
Email 92663 0
allison.mo1@monash.edu
Contact person for scientific queries
Name 92664 0
Dr Allison Mo
Address 92664 0
Transfusion Research Unit
School of Public Health and Preventive Medicine
Monash University
553 St Kilda Road
Melbourne, Victoria 3004
Country 92664 0
Australia
Phone 92664 0
+61 399030055
Fax 92664 0
Email 92664 0
allison.mo1@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not be publicly available. Grouped data will be presented in publications and presentations.
What supporting documents are/will be available?
No other documents available
Summary results
No Results