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Dutch GBS Trial

A Randomized Trial Comparing Intravenous Immune Globulin and Plasma Exchange in Guillain-Barré Syndrome

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Year of Publication: 1992

Authors: van der Meché FGA, Schmitz PIM, and the Dutch Guillain-Barré Study Group

Journal: New England Journal of Medicine

Citation: N Engl J Med 1992;326:1123-9

Link: https://doi.org/10.1056/NEJM199204233261705

Clinical Question

Is intravenous immune globulin as effective as the more complicated plasma exchange treatment in acute Guillain-Barré syndrome?

Bottom Line

IVIG is at least as effective as plasma exchange in acute Guillain-Barré syndrome and may be superior, with significantly fewer complications and greater practical advantages including availability and ease of administration.

        Major Points
        Multicenter randomized controlled trial comparing IVIG vs plasma exchange in acute GBS
150 patients randomized, 147 analyzed in interim analysis
IVIG showed 19% higher response rate at 4 weeks (53% vs 34%; P=0.024)
Median time to improve by one functional grade faster with IVIG (27 vs 41 days; P=0.05)
Significantly fewer complications with IVIG (5 vs 16 patients with multiple complications; P<0.01)
IVIG group had less need for artificial ventilation
Study stopped at interim analysis after 150 patients due to results favoring IVIG
Only age remained significant prognostic factor in multivariate analysis

      

Design

Study Type: Multicenter randomized controlled trial

Randomization: 1

Blinding: Open-label treatment; blinded outcome assessment performed by study coordinators comparing investigator scores

Enrollment Period: June 1986 to December 1989

Follow-up Duration: 182 days (6 months)

Centers: 28

Countries: Netherlands

Sample Size: 150

Analysis: Intention-to-treat; chi-square test for proportions, Mann-Whitney U test for continuous variables, Kaplan-Meier curves, multivariate logistic regression

Inclusion Criteria

Acute Guillain-Barré syndrome
Unable to walk 10 meters independently
Within two weeks of onset of neuropathy
Age ≥4 years

Exclusion Criteria

Age <4 years
Previous episode of Guillain-Barré syndrome
Previous severe allergic reaction to properly matched blood products
Known selective IgA deficiency
Treatment with immunosuppressive agents
Severe concurrent medical disease
Unavailability for follow-up for 6 months
Contraindication to plasma exchange

Arms

Field	Intravenous Immune Globulin (IVIG)	Control
Intervention	0.4 g per kilogram of body weight per day for 5 consecutive days; Gammagard (Baxter Healthcare, Hyland Division)	200-250 ml per kilogram body weight exchanged over 5 sessions within 7-14 days; replacement with 5% albumin, centrifugation or membrane techniques
Duration	5 days	7-14 days

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Improvement by one or more functional grades on a 7-point scale at 4 weeks after randomization	Primary	34%	53%	19.00%	0.024
Median time to improvement by one functional grade	Secondary	41 days	27 days		0.05
Median time to recovery of independent locomotion (functional grade 2)	Secondary	69 days	55 days		0.07
Proportion not recovering independent locomotion at 182 days	Secondary	Worse than IVIG (see Kaplan-Meier)	Better than PLEX		0.07
Days before start of treatment (median)	Secondary	1 (range 0-4)	0 (range 0-3)
Days required to complete treatment (median)	Secondary	9.5	5
Need for artificial ventilation (second week)	Adverse	42%	27%
Mean duration of intubation (days)	Adverse	22.6	15.2		<0.05
Total complications	Adverse	68 events	39 events
Patients with multiple complications	Adverse	16	5		<0.01
Pneumonia	Adverse	More common	Less common
Atelectasis	Adverse	More common	Less common
Thrombosis	Adverse	More common	Less common
Hemodynamic difficulties	Adverse	More common	Less common
Treatment-related fluctuations	Adverse	6 patients (8%)	8 patients (11%)
Liver enzyme elevation at 2 weeks	Adverse	1.02× upper limit normal (median)	2.03× upper limit normal (median)		0.02
Deaths	Adverse	2 (cardiovascular)	1 (cardiovascular)

Subgroup Analysis

Multivariate analysis showed only age was a significant independent prognostic factor (P=0.001). Distal amplitude of compound muscle action potential approached significance (P=0.053). After adjustment for center differences, overall difference favoring IVIG was 20% (95% CI 6-34%). Serologic testing showed 36% had campylobacter infection and 30% had GM-1 antibodies; neither predicted outcome.

Criticisms

Open-label treatment design
Study stopped early at interim analysis (potential overestimation of effect)
Blinding for outcome assessment was incomplete (coordinators compared scores with investigators)
Some imbalance in baseline characteristics (compound muscle action potential)
Plasma exchange techniques varied between centers
Relatively short era - may not reflect current standard of care
Three patients crossed over between treatment groups
Protocol violations occurred in 12 patients receiving plasma exchange

Funding

Baxter Healthcare Corporation, Hyland Division, and the American Red Cross

Based on: Dutch GBS Trial (New England Journal of Medicine, 1992)

Authors: van der Meché FGA, Schmitz PIM, and the Dutch Guillain-Barré Study Group

Citation: N Engl J Med 1992;326:1123-9

Content summarized and formatted by NeuroTrials.ai.

Dutch GBS Trial

(1992)

Objective

To determine whether intravenous immune globulin (IVIG) is as effective as plasma exchange in acute Guillain-Barré syndrome

Study Summary

• IVIG was at least as effective as plasma exchange (53% vs 34% improved ≥1 grade at 4 weeks; P=0.024)
• Median time to improve by one grade was 27 days (IVIG) vs 41 days (PLEX)
• IVIG had fewer complications (5 vs 16 patients with multiple complications; P<0.01)

Intervention

IVIG 0.4 g/kg/day × 5 days vs plasma exchange 200-250 ml/kg over 5 sessions within 7-14 days

Inclusion Criteria

Acute GBS, unable to walk independently, within 2 weeks of onset, age <4 years excluded

Study Design

Arms: Intravenous Immune Globulin vs Plasma Exchange

Patients per Arm: 74 IVIG vs 73 PLEX (randomized); 147 in primary analysis

Outcome

• Primary: 53% IVIG vs 34% PLEX improved ≥1 functional grade at 4 weeks (difference 19%; 95% CI 3-34%; P=0.024)
• Time to improve 1 grade: 27 days (IVIG) vs 41 days (PLEX) (P=0.05)
• Time to independent locomotion: 55 days (IVIG) vs 69 days (PLEX) (P=0.07)

Bottom Line

Major Points

Multicenter randomized controlled trial comparing IVIG vs plasma exchange in acute GBS
150 patients randomized, 147 analyzed in interim analysis
IVIG showed 19% higher response rate at 4 weeks (53% vs 34%; P=0.024)
Median time to improve by one functional grade faster with IVIG (27 vs 41 days; P=0.05)
Significantly fewer complications with IVIG (5 vs 16 patients with multiple complications; P<0.01)
IVIG group had less need for artificial ventilation
Study stopped at interim analysis after 150 patients due to results favoring IVIG
Only age remained significant prognostic factor in multivariate analysis

Study Design

Study Type: Multicenter randomized controlled trial
Randomization: Yes
Blinding: Open-label treatment; blinded outcome assessment performed by study coordinators comparing investigator scores
Sample Size: 150
Follow-up: 182 days (6 months)
Centers: 28
Countries: Netherlands

Primary Outcome

Definition: Improvement by one or more functional grades on a 7-point scale at 4 weeks after randomization

Control	Intervention	HR/OR	P-value
34%	53%	- (3% to 34% (for difference))	0.024

Limitations & Criticisms

Open-label treatment design
Study stopped early at interim analysis (potential overestimation of effect)
Blinding for outcome assessment was incomplete (coordinators compared scores with investigators)
Some imbalance in baseline characteristics (compound muscle action potential)
Plasma exchange techniques varied between centers
Relatively short era - may not reflect current standard of care
Three patients crossed over between treatment groups
Protocol violations occurred in 12 patients receiving plasma exchange

Citation

N Engl J Med 1992;326:1123-9

View Original Publication →

Dutch GBS Trial

A Randomized Trial Comparing Intravenous Immune Globulin and Plasma Exchange in Guillain-Barré Syndrome

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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