To determine whether a second IVIg course in GBS patients with a poor prognosis improves functional outcome after 4 weeks.
ID
Source
Brief title
Condition
- Autoimmune disorders
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
GBS disability score at 4 weeks after start of first IVIg course. 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
- 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 5 different time points.
Background summary
Guillain-Barré syndrome (GBS) is an immune mediated peripheral
polyradiculoneuropathy characterized by rapid onset flaccid paresis and sensory
disturbances with a very heterogenic distribution in clinical characteristics
and in prognosis. Some patients develop mild limb paresis, whereas others
develop oculomotor, facial, bulbar, respiratory muscle and limb paralysis and
remain bed bound for several months. GBS is the most frequent cause of acute
neuromuscular weakness in the Western world. It affects 1.2 persons per 100,000
per year. Intravenous immunoglobulin (IVIg) and plasma exchange (PE) are shown
to be effective in patients with GBS. These studies primarily assessed the
proportion of patients that improved 4 weeks after onset of this treatment.
Nowadays, IVIg (2 g/kg in 5 days) has become standard treatment for patients
with GBS who are unable to walk unaided and still within the first 2 weeks from
onset of weakness. The outcome of GBS after 6 or 12 months however has not, or
only marginally been improved. Approximately 20% are still disabled after 6
months, mechanical ventilation is needed in 20-30% and 3%-10% of the patients
die. Patients with severe GBS and poor prognosis may need additional or more
aggressive therapy to recover. 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 the RCT phase of this SID-GBS study is
based on this prognostic model.
There are several arguments suggesting that a second IVIg course can be
effective in patients with a poor prognosis;
1. It is known that about 10% of GBS patients only have short-lasting
improvement after a single IVIg course (*treatment-related clinical
fluctuation*), a second dose of IVIg is then followed by functional
improvement, suggesting that one IVIg course in these patients is insufficient
2. A second course of IVIg is suggested to be effective in a small uncontrolled
series of severe unresponsive GBS patients
3. Additionally, recent data from our group show that patients with a
relatively minor increase in serum IgG level after IVIg treatment recover
significantly slower and fewer patients were able to walk unaided after 6
months.
Based on these findings, it is likely that at least a proportion of GBS
patients may benefit from repeated courses of IVIg, especially the subgroup of
patients with poor prognosis.
Study objective
To determine whether a second IVIg course in GBS patients with a poor prognosis
improves functional outcome after 4 weeks.
Study design
A double-blind randomized placebo-controlled trial design will be used in
selected patients with a poor prognosis. In patients with a good prognosis the
study will have an observational design.
* All GBS patients in need of IVIg treatment, according to the treating
neurologist, in a standard dosage of 2 g/kg in 5 consecutive days are
potentially eligible for this study after obtaining informed consent.
* When patients sign *Informed consent* they principally agree to be randomized
to get a second IVIg dose or placebo when having a poor prognosis at day 7 and
to be followed up for 6 months.
* Patients with the poorest prognosis based upon the modified EGOS (mEGOS 6-12)
after the first IVIg course will be randomized to get a second course of IVIg
(Nanogam) in a dosage of 8 ml/kg (=0,4 g/kg) for 5 days or placebo (GPO) in a
dosage of 8 ml/kg for 5 days in a blinded fashion.
* mEGOS must preferentially be assessed 7 days after start of first IVIg
course, with a range to 8 or 9 days. Trial medication needs then to be started
within 24 hours when indicated according to the mEGOS score (see figure 4).
* Patient follow-up will be 6 months.
* Total patient inclusion will end when 44 patients with a poor prognosis
received a second IVIg dosage.
* After covariate adjustment, to deal with variation between patients in
baseline risk and to increase statistical power, data of the placebo group and
the intervention group will be compared
Intervention
Second IVIg treatment or placebo (GPO) in selected group of GBS patients
Study burden and risks
When patients are included in the study they will undergo the following extra
procedures;
- Throat swaps
- Blood collection
Blood collection will take place before start of standard IVIg treatment (visit
1), after standard IVIg treatment (visit 2), after two weeks (visit 3), after 4
weeks (visit 4) and after 3 months (visit 6). Mostly it will be possible to
collect blood for the study simultaneously with vena punctures performed in the
scope of the medical work-up.
- CSF collection
At admission virtually all patients undergo a lumbar puncture as part of the
standard medical workup; extra CSF will be collected for the SID-GBS study. In
this way there is no need for an extra spinal puncture. For the study a small
sample (5 cc) of CSF is sufficient. If no lumbar puncture was performed for
various reasons, no lumbar puncture will be performed in the scope of this
study.
- EMG examination generally is comparable with the situation outside a study,
but may be more extensive in some patients. This depends on the local
procedures in the participating hospitals. An EMG guideline is developed in a
way that a minimum set of nerves is tested to enable classification of
electrophysiological data according to Hadden.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Patients are diagnosed with GBS.
There is an indication to start IVIg therapy:
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 12 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, mycofenolaatmofetil, 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 CARA.
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.
Contra-indications for GPO:
proven hypersensitivity to albumin products
every situation in which hypervolaemia or haemodilution can form a special risk; examples of such conditions are: heart failure, severe hypertension, oesophageal varices, pulmonary oedema, haemorrhagic diathesis, severe anaemia, renal and postrenal anuria
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2008-005659-83-NL |
| CCMO | NL26512.078.09 |