What is RATIONALISE?
Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension (RATIONALISE)
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RATIONALISE is a clinical trial being conducted in collaboration with hospital sites across Australia and New Zealand.
Some blood cancers, or the medications used to treat them, can lead to hypogammaglobulinemia (low levels of immunoglobulin [antibodies] in the blood), resulting in an increased risk of serious infection. To treat this condition, patients are often given immunoglobulin (antibodies) to prevent serious infection.
The trial aims to address evidence gaps in immunoglobulin (Ig) use and infection prevention in patients with blood cancer. In particular, the trial is investigating whether it is safe to stop immunoglobulin replacement therapy if patients have been free of major infection for 6 months, and whether prophylactic antibiotics should be administered once the therapy is stopped.
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The need for a clinical trial
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Studies supporting immunoglobulin use were conducted 20-30 years ago and we do not know the effects of immunoglobulin given to patients in the context of newer anti-cancer treatments.
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There is variation in the international guidelines on when to administer immunoglobulin, and this is reflected in the different practice for immunoglobulin administration between different countries.
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The optimal duration of immunoglobulin use is not clearly defined. The international guidelines vary considerably in their recommendations for if and when to trial a cessation of immunoglobulin.
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Immunoglobulin is made from donated plasma, and it is expensive, so must be used wisely. The demand for immunoglobulin is also increasing, leading to increased challenges for meeting demand.
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There is some evidence to support the rationale for using prophylactic oral antibiotics to treat patients with acquired hypogammaglobulinemia but their use in this context needs to be properly evaluated.
Overview
RATIONALISE is a Phase II/III randomised controlled trial enrolling participants with acquired hypogammaglobulinemia secondary to haematological malignancy (chronic lymphocytic leukaemia, multiple myeloma, or non-Hodgkin's lymphoma).
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Eligible participants will be allocated on a 1:1:1 ratio to one of three treatment groups:
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Stop immunoglobulin and commence daily prophylactic oral antibiotics
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Stop immunoglobulin and prescribed antibiotics to keep at home to use immediately if symptoms of infection develop, with immediate review by treating clinical team, nearest emergency department or medical practitioner
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Continue to receive intravenous or sub-cutaneous immunoglobulin as per current treatment regimen
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RATIONALISE aims to find out:
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If immunoglobulin therapy can be ceased after six months if patients are free of major infection, and,
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If after immunoglobulin cessation, whether patients should take prophylactic oral antibiotics
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The primary outcome of the trial is event-free survival, defined from the date of randomisation until the earliest date of occurrence of Grade 3 or higher infection (as per CTCAE version 5) as reviewed by an Outcome Adjudication Committee, or death from any cause.
Sub-studies
​Led by Dr Laura Fanning and Prof Dennis Petrie, Centre for Health Economics, Monash University:
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A health-economic analysis will be conducted to assess the cost-effectiveness of the trial interventions.
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Led by Dr Khai Li Chai and Dr Catriona Parker, Transfusion Research Unit, Monash University:
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A qualitative study will explore patient perspectives on the use of immunoglobulin and oral antibiotics.
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Led by Prof Orla Morrissey, Department of Infectious Diseases, Monash University:
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Blood and faecal samples will be collected and sent to a central lab for testing. Samples will be analysed to better understand immune function in this patient group.
Find out more
For further information and all general trial-related enquiries, please contact the Monash University Project Team
Alternatively, comprehensive trial information, including participating hospital sites can be found on the
The RATIONALISE trial is sponsored by Monash University and is being conducted in collaboration with the Australasian Leukaemia and Lymphoma Group (ALLG). The trial forms part of the NHMRC Blood Synergy Program.
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RATIONALISE Coordinating Principal Investigators:
Prof Zoe McQuilten
Prof Erica Wood
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Trial Coordinating Centre:
The trial is being centrally coordinated by the Transfusion Research Unit within the School of Public Health and Preventive Medicine at Monash University.
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Committees:
The project team would like to acknowledge the contribution of the membership of the following committees:
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Trial Steering Committee
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Data and Safety Monitoring Committee
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Outcome Adjudication Committee
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RATIONALISE is funded by an NHMRC '2020 Clinical Trials and Cohort Studies' grant and has received ethics approval to be conducted at participating sites within Australia from the Monash Health Human Research Ethics Committee.