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Trial registered on ANZCTR


Registration number
ACTRN12624000961549
Ethics application status
Approved
Date submitted
5/07/2024
Date registered
8/08/2024
Date last updated
27/10/2024
Date data sharing statement initially provided
8/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Platform Trial (RATIONAL-PT)
Scientific title
A randomised platform trial evaluating the role of interventions to prevent infection in patients with acquired hypogammaglobulinemia secondary to haematological malignancies - RATIONAL-PT (Core)
Secondary ID [1] 312171 0
TRU-RPT-22
Universal Trial Number (UTN)
Trial acronym
RATIONAL-PT
Linked study record
ACTRN12624000964516: The 'Start-Ig' Domain of RATIONAL-PT.
ACTRN12624000963527: The 'Stop-Ig' Domain of RATIONAL-PT.
ACTRN12624000962538: The 'Dose-Ig' Domain of RATIONAL-PT.
ACTRN12616001723471: The RATIONAL Trial was a feasibility trial which is now completed and informed the development of the RATIONAL-PT, and in particular the Start-Ig domain.
ACTRN12622000359730: The RATIONALISE trial is an ongoing trial and related to the Stop-Ig domain.

Health condition
Health condition(s) or problem(s) studied:
haematological malignancy 333821 0
hypogammaglobulinemia 333822 0
Condition category
Condition code
Cancer 330492 330492 0 0
Myeloma
Cancer 330493 330493 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 330494 330494 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This research project uses an Adaptive Platform Design. This design allows the researchers to compare multiple infection prevention strategies within the same trial at the same time (rather than running separate trials), to analyse results as the trial occurs and to add new research questions during the course of the trial.

Initially the researchers will be investigating how safe and effective immunoglobulin replacement therapy is compared to oral antibiotics to prevent serious infections in patients with blood cancers, and also comparing different approaches to immunoglobulin dosing to determine the best dose of immunoglobulin for infection prevention. Further comparisons may be added to the platform.

Each comparison will be included as a sub-component, or ‘domain’, of the RATIONAL-PT. The treatments used in each domain may not be the same. Examples of treatments may include intravenous immunoglobulin, sub-cutaneous immunoglobulin and oral antibiotics. The duration of the trial-related treatment is 12 months in each domain.

Investigational products to be trialled will be considered and approved by the International Trial Steering Committee (ITSC). The ITSC will include members with experience and knowledge of the trial design, domain-specific expertise and regional-specific expertise.

Participants who have enrolled in and completed one domain may be invited to participate in another domain appropriate to their changed status. Each domain has its own domain-specific selection criteria, therefore eligibility for one domain does not imply eligibility for other domains.

The anticipated duration of the trial is 5 years. However, due to the adaptive platform design, trial duration may be extended in future with the addition of new domains.
Intervention code [1] 328626 0
Treatment: Drugs
Comparator / control treatment
Not applicable.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338266 0
Event-free survival (EFS), defined as time from randomisation (or, in domains with a single treatment arm, time from registration) until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause.
Timepoint [1] 338266 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [1] 435201 0
Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months
Timepoint [1] 435201 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [2] 435202 0
Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Timepoint [2] 435202 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [3] 435203 0
Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Timepoint [3] 435203 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [4] 435204 0
Occurrence of one or more microbiologically documented infections from randomisation to 12 months.
Timepoint [4] 435204 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [5] 435205 0
Number of microbiologically documented infections from randomisation to 12 months.
Timepoint [5] 435205 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [6] 435206 0
All-cause mortality at 12 months
Timepoint [6] 435206 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [7] 435207 0
Infection-related mortality at 12 months
Timepoint [7] 435207 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [8] 435208 0
Time free from hospitalisation with antimicrobial administration with therapeutic intent from randomisation to 12 months.
Timepoint [8] 435208 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [9] 435209 0
Occurrence of one or more treatment-related adverse events
Timepoint [9] 435209 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [10] 435210 0
Number of treatment-related adverse events.
Timepoint [10] 435210 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [11] 435211 0
Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months.
This will be assessed as a composite outcome.
Timepoint [11] 435211 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [12] 435212 0
Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated from randomisation to 12 months.
This will be assessed as a composite outcome.
Timepoint [12] 435212 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)
Secondary outcome [13] 435213 0
Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the EQ-5D-5L questionnaire.
Timepoint [13] 435213 0
Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation
Secondary outcome [14] 435218 0
Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the EORTC QLQ-C30 questionnaire.
Timepoint [14] 435218 0
Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation
Secondary outcome [15] 435219 0
Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the FACT-N questionnaire.
Timepoint [15] 435219 0
Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation.
Secondary outcome [16] 435220 0
Costs associated with allocated treatment arm and infections during study. This will be assessed as a composite outcome.
Timepoint [16] 435220 0
12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Eligibility
Key inclusion criteria
1. Aged greater than or equal to 18 years of age
2. Diagnosis of haematological malignancy, including CLL, MM or NHL
3. Eligible to receive or currently receiving Ig (IV or subcutaneous - SCIg) replacement for history of recurrent or severe infection(s) and IgG less than the lower limit of the reference range (excluding paraprotein) OR IgG<4g/L (excluding paraprotein)
4. Life expectancy > 12 months
5. Able to give informed consent

Additional eligibility criteria will apply for each domain of the RATIONAL Platform Trial.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treating team deems enrolment in the study is not in the best interests of the patient

Additional eligibility criteria will apply for each domain of the RATIONAL Platform Trial.

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
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The RATIONAL Platform Trial (RATIONAL-PT) provides the framework on which different interventions and domains exist within the trial. The domains linked to the platform detail the specific interventions to be studied within that domain and whether or not randomisation will be used for treatment allocation.
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Up to 900 participants will be recruited to the RATIONAL-PT, including up to 300 per domain. The aim of the platform is to determine optimal supportive care interventions for patients with haematological malignancies. The primary outcome for the platform is Event-free survival (EFS), defined as time from randomisation (or, in domains with a single treatment arm, time from registration) until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause. Data from each domain will contribute to the primary analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
900
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,SA,VIC

Funding & Sponsors
Funding source category [1] 316537 0
Government body
Name [1] 316537 0
National Health and Medical Research Council
Country [1] 316537 0
Australia
Funding source category [2] 316539 0
Government body
Name [2] 316539 0
Australian Department of Health and Aged Care, Medical Research Future Fund (MRFF)
Country [2] 316539 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Country
Australia
Secondary sponsor category [1] 318720 0
None
Name [1] 318720 0
NA
Address [1] 318720 0
Country [1] 318720 0
Other collaborator category [1] 283040 0
Other Collaborative groups
Name [1] 283040 0
Australasian Leukaemia & Lymphoma Group (ALLG)
Address [1] 283040 0
Country [1] 283040 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315330 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315330 0
https://www.alfredhealth.org.au/research/ethics-research-governance
Ethics committee country [1] 315330 0
Australia
Date submitted for ethics approval [1] 315330 0
13/11/2023
Approval date [1] 315330 0
04/01/2024
Ethics approval number [1] 315330 0
HREC/103986/Alfred-2023 (Local Reference: Project 726/23)

Summary
Brief summary
This study is being conducted to find out how safe and effective different strategies of infection prevention are in comparison to each other, for preventing infection in patients with blood cancers.

Who is it for?
Patients with a blood cancer and low levels of certain antibodies (immunoglobulins) in the blood.
Your treating doctor will check your eligibility to participate in this study. You will need to undergo screening assessments to find out if it is safe for you to be involved in the study.

Study details:
This research project uses an Adaptive Platform Design. This design allows the researchers to compare multiple infection prevention strategies within the same trial at the same time (rather than running separate trials), to analyse results as the trial occurs and to add new research questions during the course of the trial.

The treatments that you may receive as part of the study will be determined by which domain(s) of the platform you participate in. Depending on the domain you are participating in, you may be assigned to a study treatment by chance (randomly). Following randomisation (if applicable), you will be asked to complete your Day 1 assessments.

If eligible to participate in a domain of the RATIONAL-PT, your active study participation in that domain will last for 13 months and all participants will return to the hospital for a study visit every 3 months (4 more in-person visits after Day 1). During each month of the 12-month treatment period except the months in which you are attending in-person study visits, you will receive a phone call from your treating clinical team to check your progress (8 calls in total).

Even if you are recommended to, or choose to, stop your domain treatment during the 12-month treatment period, you will be asked to continue attending study visits and having phone calls until the end of the trial period (13 months in total) because we are still interested in your outcomes.

At the end of your participation on the study, your doctor will decide if you still require treatment to prevent infection, and if you do, whether to continue on the treatment you received during the study (immunoglobulins, antibiotics or none).

The results of this trial will inform clinical decision making about the use of immunoglobulin and oral antibiotics for patients with blood cancers. Your participation may help doctors who treat patients with blood diseases in the future to know which treatment to prescribe to try to prevent serious infections.
Trial website
Trial related presentations / publications
Public notes
The RATIONAL-PT trial includes the following optional sub-studies:

- Qualitative Sub-Study: The purpose of this sub-study is to explore your experiences of immunoglobulins, antibiotics and other treatments that affect infection risk. If you agree to take part, you will be asked to participate in a one-to-one interview. Your responses and views will help us build a more complete picture of preferences of treatments used to reduce infection from a patient's perspective.

- Pharmacokinetic/Pharmacodynamic (PK/PD) Sub-Study: The purpose of this sub-study is to better understand what dose of immunoglobulin is likely to provide the greatest benefit to patients. This sub-study will require additional blood samples which will be drawn at various timepoints around a single dose of immunoglobulin. By measuring the amount of immunoglobulin in your blood at different timepoints, it will help to determine how long it takes for immunoglobulin to be absorbed into your body, how long it stays in the body after it has been absorbed, and the relationship between the amount in the body and its effect on the body.

- Patient Preferences Sub-study: The purpose of this sub-study is to explore your preferences for treatments that affect infection risk. If you agree to participate you will be asked to complete an online survey. During the survey we will ask you to imagine making choices between different treatment options for preventing infection based on different aspects of the treatment (for example, how often it is administered, how long it takes to administer, the likelihood of side effects, risk of infection and out-of-pocket costs and so on).

RATIONAL-PT participants may be invited to participate in one or more of the above sub-studies. Participation is optional and participants may still participate in RATIONAL-PT even if they choose not to participate in any or all of the sub-studies.

Contacts
Principal investigator
Name 134362 0
Prof Zoe McQuilten
Address 134362 0
Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004
Country 134362 0
Australia
Phone 134362 0
+61 3 9903 0379
Fax 134362 0
Email 134362 0
[email protected]
Contact person for public queries
Name 134363 0
Zoe McQuilten
Address 134363 0
Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004
Country 134363 0
Australia
Phone 134363 0
+61 3 9903 0379
Fax 134363 0
Email 134363 0
[email protected]
Contact person for scientific queries
Name 134364 0
Zoe McQuilten
Address 134364 0
Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004
Country 134364 0
Australia
Phone 134364 0
+61 3 9903 0379
Fax 134364 0
Email 134364 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
Individual participant data will not be publicly available. Data will only be presented as a whole, no individual data will be published or presented.


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.