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Trial registered on ANZCTR


Registration number
ACTRN12621000815864
Ethics application status
Approved
Date submitted
13/04/2021
Date registered
28/06/2021
Date last updated
4/07/2022
Date data sharing statement initially provided
28/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Is therapeutic plasma exchange a better treatment than intravenous immunoglobulin in people with severe Guillain-Barre Syndrome (GBS)?
Scientific title
Does therapeutic plasma exchange improve outcomes in severe Guillain-Barre Syndrome (GBS) compared to intravenous immunoglobulin? A protocol for a New Zealand pilot study
Secondary ID [1] 303889 0
None
Universal Trial Number (UTN)
Trial acronym
IRIS
Linked study record
n/a

Health condition
Health condition(s) or problem(s) studied:
Guillain-Barre Syndrome (GBS) 321465 0
Condition category
Condition code
Neurological 319229 319229 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Therapeutic plasma exchange (TPE): is a semi-automated extracorporeal procedure to exchange the plasma with an inert blood replacement such as Albumin. This helps in the progressive dilution of immunoglobulins which are the presumed target in an autoimmune condition.

IRIS TRIAL - THERAPEUTIC PLASMA EXCHANGE PROTOCOL

Machine:
• Centrifugal apheresis machine

Procedure:
• 5 – 7 procedures in 7 – 10 days, on alternate days
• Initial exchange: 1.2 to 1.5 times Total Plasma Volume (TPV), 90-120 minutes per session
• Subsequent exchanges: 1.0 TPV
• Replacement solution: 4% Albumin only

Monitoring:
• At initiation: FBC, Coag Screen, U& E’s, Liver Function tests
• Daily coagulation screen in the morning before the procedure
• Every patient to be put on Vit K 10mg IV, daily prophylactically


The decision of whether or not a participant receives 5, 6 or 7 procedures will be the decision of the "treating" neurologist/clinician (i.e.not the "study" neurologist/research team) to ensure that the care of the patient is kept independent from the study objectives.
Intervention code [1] 320197 0
Treatment: Drugs
Intervention code [2] 320513 0
Treatment: Other
Comparator / control treatment
The active control group is intravenous immunoglobulin.

IRIS TRIAL - Intravenous Immunoglobulin Protocol
Product:
• Intragam P or Privigen
Initial Dose:
• 2 gms/ Kg – divided over 2 - 5 days
• Can be adjusted to ideal body weight for patients who weigh > 100 kg
Second Dose:
• 2 gms/ Kg – divided over 2 - 5 days
• Can be adjusted to ideal body weight for patients who weigh > 100 kg
• Only to be considered for situations where there was initial improvement but was followed by subsequent deterioration post first IVIG treatment
Procedure:
• Follow local institutional policy & protocol on authorisation for ordering IVIG, e.g. IGO on-line approval or equivalent
• Send a FBC & baseline U&E’s, LFTs and Coagulation screen samples
• Once a week FBC should be done for a month following initiation of treatment with IVIG
• Send a sample to Blood Bank for a basic blood group & antibody screen before initiation of treatment with IVIG
• Follow local institutional policy for the administration of Intragam P or Privigen
• Please report adverse reactions to local Blood Bank & Haemovigilance


- The decision of whether or not a participant receives doses over 2-5 days will be the decision of the "treating" neurologist/clinician (i.e.not the "study" neurologist/research team) to ensure that the care of the patient is kept independent from the study objectives.
- The second dose occurs 24 hours after the first dose.
Control group
Active

Outcomes
Primary outcome [1] 327100 0
The primary composite outcome will be the number of days in high dependency unit (HDU) and/or ICU.

Method of assessment: assessed by accessing patient medical records, date of admission and discharge from HDU/ICU will be recorded on the Case Report Form.
Timepoint [1] 327100 0
Time of discharge from ICU/HDU.
Secondary outcome [1] 393788 0
1. Mortality
2. Method of assessment: assessed by accessing patient medical records
Timepoint [1] 393788 0
Any time up to 6 months.
Secondary outcome [2] 395172 0
Time on assisted mechanical ventilation (assessed by accessing patient medical records).
Timepoint [2] 395172 0
Any time up to 6 months.
Secondary outcome [3] 395173 0
Strength

Measured by the Rasch-modified summer Medical Research Council score.
Timepoint [3] 395173 0
Assessed at initial study assessment, 1 week after starting treatment, 1, 3 and 6 months after starting treatment.
Secondary outcome [4] 395174 0
Function

Measured by the Inflammatory Neuropathy Cause and Treatment (INCAT) score and the Hughes GBS disability scale,

This is a composite secondary outcome
Timepoint [4] 395174 0
Assessed at initial study assessment, 1, 3 and 6 months after starting treatment.
Secondary outcome [5] 395175 0
Fatigue

Measured by the Rasch-built fatigue severity scale
Timepoint [5] 395175 0
Assessed at initial study assessment, 1, 3 and 6 months after starting treatment.
Secondary outcome [6] 395176 0
Quality of life

Measured by EurQol EQ-5D Health Questionnaire.
Timepoint [6] 395176 0
Assessed at 6 months

Eligibility
Key inclusion criteria
Inclusion criteria:
1) A diagnosis of GBS by Cornblath and Asbury criteria .
2) GBS severity of 4 or 5 by Hughes GBS severity scale OR early treatment outcome (EGOS) score of 5 or greater OR early GBS respiratory insufficiency (EGRIS) score of 5 or greater.
3) Able to start assigned treatment within 2 weeks of weakness onset.
4) At least 18 years of age at the time of enrollment.
5) Able to provide informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:
1) Any antecedent illness that would interfere with the ability to perform outcome assessments
2) History of an allergy to IVIg
3) History of an allergic reaction to Albumin 4%.
4) History of IgA deficiency with anti-IgA antibodies
5) Known reaction to blood products
6) Patient with strong objection to the use of blood products

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features


Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Regarding primary outcomes, differences between the mean number of days spent in HDU/ICU between Group A (IVIG) and Group B (TPE) will be compared between randomised groups using the non-parametric Mann-Whitney U test. Regarding secondary outcomes, the secondary outcomes will be compared between randomised groups using the non-parametric Mann-Whitney U test or independent t-tests depending on the scale of the outcome measure. A two-tailed p-value <0.05 will be taken to indicate statistical significance

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/07/2021
Actual
Date of last participant enrolment
Anticipated
3/07/2023
Actual
Date of last data collection
Anticipated
29/12/2023
Actual
Sample size
Target
50
Accrual to date
0
Final
Recruitment outside Australia
Country [1] 23583 0
New Zealand
State/province [1] 23583 0
Waikato/Wellington/Auckland

Funding & Sponsors
Funding source category [1] 308279 0
Charities/Societies/Foundations
Name [1] 308279 0
Waikato Medical Research Foundation Grant
Country [1] 308279 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato Hospital
Address

183 Pembroke Street
Hamilton 3240
NEW ZEALAND
Country
New Zealand
Secondary sponsor category [1] 309081 0
None
Name [1] 309081 0
Address [1] 309081 0
Country [1] 309081 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308254 0
Health and Disability Ethics Committees (HDECs)
Ethics committee address [1] 308254 0
Postal address:
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Street address:
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 308254 0
New Zealand
Date submitted for ethics approval [1] 308254 0
16/04/2021
Approval date [1] 308254 0
08/06/2021
Ethics approval number [1] 308254 0

Summary
Brief summary
This is a prospective, rater-blinded, randomised pilot study to compare the outcome of severe GBS patients (Hughes GBS Disability Scale 4 and 5) treated with TPE vs those patients treated with IVIg.

We hypothesise that TPE will lead to improved outcomes in comparison to IVIg therapy in patients with severe GBS
Trial website
n/a
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110090 0
Dr Eileen Mc Manus
Address 110090 0
Neurology Department
Waikato Hospital
183 Pembroke street
Hamilton
3204
Country 110090 0
New Zealand
Phone 110090 0
+642108740678
Fax 110090 0
Email 110090 0
[email protected]
Contact person for public queries
Name 110091 0
Eileen Mc Manus
Address 110091 0
Neurology Department
Waikato Hospital
183 Pembroke street
Hamilton
3204
Country 110091 0
New Zealand
Phone 110091 0
+642108740678
Fax 110091 0
Email 110091 0
[email protected]
Contact person for scientific queries
Name 110092 0
Eileen Mc Manus
Address 110092 0
Neurology Department
Waikato Hospital
183 Pembroke street
Hamilton
3204
Country 110092 0
New Zealand
Phone 110092 0
+642108740678
Fax 110092 0
Email 110092 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
there is no indication to share raw data outside investigator team.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11341Study protocol    381758-(Uploaded-13-04-2021-05-30-56)-Study-related document.doc



Results publications and other study-related documents

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