Primary objectiveTo determine whether a second IVIg dose in GBS patients with a poor prognosis improves functional outcome after 4 weeks.Secondary objectives To investigate whether: - a second IVIg dose in GBS patients with a poor prognosis improves…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoint
GBS disability score at 4 weeks after start of first IVIg dose. The full range
of scores will be considered as an ordinal outcome scale. In analyzing we will
use a proportional odds model. (Extent of) improvement on this ordinal scale
will be compared between groups.
Secondary outcome
Secondary study endpoints
- Percentage of patients that improve:
at least 1, 2, 3 or 4 points on the GBS disability score at 4, 8, 12 and 26
weeks,
at least 4, 8 or 12 points on MRC sum score (ranging from 0-60) at 4, 8, 12
and 26 weeks,
at least 2, 4 or 6 points on ONLS score (ranging from 0-12) at 4, 8, 12 and
26 weeks.
- Percentage of patients needing artificial ventilation.
- Time (number of days) on respirator.
- Time (number of days) on intensive care unit.
- Percentage of patients that die because of GBS.
- Time (number of days) to hospital discharge.
- Percentage of patients with secondary deterioration due to treatment-related
fluctuations (TRF).
- Development of complications possibly related to a second IVIg course.
- Serum IgG levels at 4 different time points.
Other study parameters
- To correct for known prognostic factors (age, preceding diarrhea, positive
serology of different micro-organisms, antibodies against gangliosides) we will
ask questions about antecedent events, as diarrhea and upper respiratory tract
infection and perform laboratory measurements (serology against Campylobacter
jejuni, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Mycoplasma pneumonia
and IgG, IgM and IgA antibodies against GM1, GD1a and GQ1b).
Background summary
Guillain-Barré syndrome (GBS) is the most frequent cause of acute neuromuscular
weakness in the Western world that can occur at any age. GBS is a rapidly
progressive *inflammatory* disorder of the peripheral nerves often leading to a
severe paresis of arms and legs. Most GBS patients also have sensory
disturbances (tingling or dull feeling) and pain. Some patients also have
double vision or problems with swallowing. GBS may also involve the respiratory
muscles, leading to insufficient respiration and admission on an intensive care
unit. About 25% of patients need artificial respiration for a period ranging
from weeks to several months. Progression of weakness in GBS is fast and
reaches its maximum within 4 weeks (by definition), but the maximum is
generally reached within 2 weeks. Thereafter the patients have a variable
prognosis. GBS is mostly preceded by a common infection with Campylobacter or
an upper respiratory tract infection. Auto-reactive antibodies play a role in
the pathogenesis of the disorder. GBS is - at least partially - a treatable
disorder. Intravenous immunoglobulin (IVIg) 2 g/kg administered in 5 days (one
*dose*) was shown to be effective when applied within the first two weeks after
onset of weakness, and nowadays is the treatment of choice. Although treatment
with a standard single dosage of IVIg improves outcome, recovery from GBS often
is far from good. Patients with severe GBS and poor prognosis may need
additional or a more aggressive therapy to recover. Careful selection of
patients eligible for extra therapy is important, because extra treatment
entail added complication risks and costs. Multiple clinical,
electrophysiology, serological and laboratory factors have been identified as
predictors for poor outcome. These include older age, rapid disease
progression, preceding diarrhoea/Campylobacter jejuni serology, absence of
antecedent upper respiratory tract infection, axonal EMG and anti-GM1
antibodies. A recent study showed that the prognosis of individual GBS patients
can accurately be predicted based on three simple clinical factors that can
easily be obtained early during the course of disease. The selection of
patients for a second IVIg course in hospitals were this is common practice is
based on this prognostic model.
The I-SID GBS study will be conducted in cooperation with the Inflammatory
Neuropathy Consortium (INC). The INC is a worldwide network of neurologists
interested to study patients with immune-mediated neuropathies, including GBS.
The INC is a working group of the Peripheral Nerve Society (www.PNSociety.com).
Members of the INC have been informed by email about this I-SID GBS study. A
questionnaire was sent to invent the local IVIg treatment policy in GBS
patients among neurologists in different places around the world. According to
this questionnaire (response, n=27) 25-50% of the centers treat patients with a
poor prognosis already with a second dose of IVIg. However, 96% of the
neurologists considered it ethical to randomise GBS patients with a poor
prognosis for a second IVIg dose, because the effect this additional IVIg
treatment has not been investigated yet. The I-SID GBS study is a prospective
international multicenter observational study in which (based on logistics and
a limited budget) no randomisation will take place. This has been discussed
extensively within the INC.Treatment policy is at full discretion of the
individual center. The centers will be asked prior to start of the study
whether they are used to treat patients with a poor prognosis (based upon the
mEGOS prognostic model) with a second dose IVIg or not and are asked to do the
same in this I-SID GBS study.
Study objective
Primary objective
To determine whether a second IVIg dose in GBS patients with a poor prognosis
improves functional outcome after 4 weeks.
Secondary objectives
To investigate whether:
- a second IVIg dose in GBS patients with a poor prognosis improves functional
outcome or muscle strength after 8, 12 and 26 weeks.
- a second IVIg dose in GBS patients with a poor prognosis lowers the
percentage of patients needing artificial ventilation, lower the time (number
of days) on respirator or time on the intensive care.
- a second IVIg dose in GBS patients with a poor prognosis reduces the time to
hospital discharge.
- a second IVIg dose in GBS patients with a poor prognosis reduce the chance of
secondary deterioration due to treatment-related fluctuations.
- patients treated with a second IVIg dose develop more complications possibly
related to the second IVIg treatment.
- a second IVIg dose in GBS patients with a poor prognosis lowers the
percentage of patients that die because of GBS.
- serum IgG increase after the first IVIg dose is lower in patients with a poor
prognosis.
- serum IgG increases further (and to what extent) after a second IVIg dose in
relation to prognosis.
Study design
A prospective international multicenter observational study design will be
used.
All GBS patients in need of IVIg treatment, according to the treating
neurologist, in a standard dose of 2 g/kg in 2-5 consecutive days, are
potentially eligible for this study after obtaining informed consent.
• When patients sign *Informed Consent* they principally agree to be followed
up for this I-SID GBS study for a period of 6 months.
• Patients with the poorest prognosis based upon the mEGOS (score 6-12) after
the first IVIg dose are treated with a second dose of IVIg in the same dosage
as the initial IVIg treatment or receive no additional treatment, according to
the local treatment policy.
• mEGOS must preferentially be assessed 7 days after start of first IVIg dose
with a range to 8 or 9 days. A second IVIg dose (in patients with mEGOS 6-12)
preferentially should be started within 24 hours after determining the mEGOS
score at day 7 (max 8-9).
• Patient follow-up will be 6 months.
• Patient inclusion will end when 300 patient (whole range of severity) were
included, this is likely to be feasible with approximately 3 years of accrual.
Study burden and risks
Patients will undergo extra blood sampling because of the study participation.
Blood sampling will take place before start of standard IVIg treatment, after
standard IVIg treatment, after two weeks, after 4 weeks and after 3 months.
Mostly it will be possible to collect blood for the study simultaneously with
vena punctures performed in the scope of the medical work-up.
Dr. Molewaterplein 50-60
3015 GE Rotterdam
NL
Dr. Molewaterplein 50-60
3015 GE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
• Patients are diagnosed with GBS according to NINDS diagnostic criteria.(3)
• Indication to start IVIg treatment:
1. Patient is unable to walk unaided for >10 meter (grade 3, 4 or 5 of the GBS disability scale)
or
2. There is otherwise an indication to start IVIg treatment according to the treating neurologist
• Onset of weakness due to GBS is less than 2 weeks ago.
• Signed informed consent.
Exclusion criteria
• Age less than 6 years
• Patient known to have a severe allergic reaction to properly matched blood products or plasma products.
• Pregnancy or breastfeeding.
• Patient known to have a selective IgA deficiency.
• Patient shows clear clinical evidence of a polyneuropathy caused by e.g. diabetes mellitus (except mild sensory), alcoholism, severe vitamin deficiency, porphyria.
• Patient received immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycofenolatemofetil, tacrolimus, sirolimus or > 20 mg prednisolon daily) during the last month.
• Patient known to have a severe concurrent disease, like malignancy, severe cardiovascular disease, AIDS, severe COPD.
• Inability to attend follow-up during 6 months.
Relative contra-indications for second IVIg dose:
• Patients known to have severe kidney dysfunction (GFR below 40 ml/min).
• Pre-existing risk factors of thrombo-embolic complications or severe ischemic heart disease.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL38252.078.11 |