Intravenous immunoglobulin overtreatment in chronic inflammatory demyelinating polyneuropathy

Plain English Summary

Background and study aims
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neuropathy that can lead to considerable disability (walking difficulties and loss of arm dexterity.) Intravenous immunoglobulin (IVIg) is an effective treatment for CIDP. There is however no evidence on how long the treatment should last. This is particularly challenging given the variable and unpredictable course of the disease. In some patients currently treated with IVIg, the disease is actually not active and further treatment is not necessary. Several recent studies have confirmed that there is overtreatment with IVIg. Unfortunately, the only way currently to assess whether treatment is needed is to try and stop treatment. Because of the fear of deterioration in IVIg-dependent patients, attempts to reduce IVIg treatments are not performed frequently. In this study we aim to quantify and reduce overtreatment with IVIg in patients with CIDP. We will introduce a standardised IVIg restabilisation protocol to limit the increase in disability in participants who turn out to be IVIg-dependent. We will explore possible predictors of IVIg dependency to guide long-term IVIg treatment in the future.

Who can participate?
Adult patients with CIDP currently receiving maintenance IVIg infusions are eligible for this study.

What does the study involve?
Participants will be randomly allocated to oe of two groups: IVIg withdrawal group or continuation of IVIg treatment group. Participants in IVIg withdrawal group will start with a tapering phase consisting of 3 infusions which will be followed by 100% placebo infusions. Participants in continuation of IVIg treatment group will receive the same IVIg treatment as before the study. All treatments will be provided by home-care nurses. Subjects will be followed for at least 24 weeks after inclusion.

What are the possible benefits and risks of participating?
Successful IVIg withdrawal will reduce adverse events, the discomfort caused by regular infusions and related health care costs. The main risk is deterioration during the study. Participants will be closely monitored, IVIg treatment will be resumed if the participant’s condition gets worse and the increase in disability will be limited to a very short time period.

Where is the study run from?
Participants will be recruited from Dutch neuromuscular centers.

When is the study starting and how long is it expected to run for?
The study will start in April 2014 and is expected to run until October 2016, including a 24-week follow-up period.

Who is funding the study?
Dutch Governmental grant and by Sanquin Blood Supply.

Who is the main contact?
Dr Filip Eftimov
f.eftimov@amc.uva.nl

Study website

Type

Scientific

Contact name

Dr Filip Eftimov

ORCID ID

Contact details

Academic Medical Centre
Department of Neurology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
-
f.eftimov@amc.uva.nl

EudraCT/CTIS number

2013-005363-52

IRAS number

ClinicalTrials.gov number

Protocol/serial number

IOC

Scientific title

Intravenous immunoglobulin overtreatment in chronic inflammatory demyelinating polyneuropathy: a randomized controlled non-inferiority trial

Acronym

IOC (IVIg Overtreatment in CIDP)

Study hypothesis

The hypothesis is that there is overtreatment in patients receiving long-term maintenance intravenous immunoglobulin (IVIg) treatment. The primary objective of the study is to determine whether subjects with chronic inflammatory demyelinating polyneuropathy (CIDP) are overtreated with maintenance IVIg treatment and to reduce overtreatment-associated subjects’ burden and healthcare costs.

Ethics approval(s)

Medical Ethical Committee of the Academic Medical Center, 18/03/2014, Ref: 2014-018#B2014239a

Study design

Multicentre randomized double-blind standard treatment-controlled non-inferiority trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Intervention

Subjects will be randomised to one of the following two treatments:
1. IVIg withdrawal (tapering consists of three infusions (75%, 50% and 25% respectively of the subjects’ pre-study IVIg dose combined with placebo), which will be followed by 100% placebo infusions. Placebo will consist of sodium chloride (0.9%) in comparable amounts and intervals as the previous IVIg treatment.
2. Comparative treatment will be the standard treatment, in which subjects will receive the same IVIg infusions (dose and interval) as prior to the study.

Intervention type

Other

Primary outcome measure

The change between baseline and endpoint Rasch-Overall Disability Score (R-ODS). An endpoint will be reached in case of one of the following: final visit at 24 weeks or deterioration on the R-ODS by more than 0.652 logits during follow-up.

Secondary outcome measures

1. The proportion of subjects remaining stable on their individual R-ODS score and completing the follow-up period. An individual subject will be considered stable if the difference between his or her baseline and endpoint R-ODS scores is less than 0.652 logits.
2. Muscle strength using the Medical Research Council (MRC) sum score of 12 predefined muscle groups (range 0 to 60, including shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and foot dorsiflexion).
3. Grip strength, measured in kPa by a Martin vigorimeter.
4. Sensory impairment using the modified INCAT Sensory Sum Score (INCAT–SS, range 0-20).
5. Subject’s perception of clinical deterioration on a 5-point Likert scale.
6. Disease-non-specific disability using the AMC Linear Disability Scale (ALDS, range 0 [dead] to 100 [fully able]).
7. Quality of life using Short Form-36 (SF-36).
8. Pain using the Pain-Intensity Numerical Rating Scale (PI-NRS, an 11-point scale).
9. Fatigue using a 7-item linear modified Rasch-built fatigue scale.
10. Costs of healthcare use, costs of production loss, and out-of-pocket expenses.
11. Difference between serum IgG levels before and after last IVIg infusion prior to first study treatment

All secondary outcomes will be measured when an endpoint is reached. An endpoint will be reached in case of one of the following:
1. Final visit at 24 weeks
2. Deterioration on the R-ODS by more than 0.652 logits during follow-up

Overall study start date

01/04/2014

Overall study end date

31/07/2019

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Probable or definite CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria 2010
2. Stable disease for 6 months (i.e., no progression of disease in the last 6 months)
3. IVIg treatment for at least 6 months
4. IVIg infusion interval of 2 to 6 weeks
5. Age > 18 years

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

60

Total final enrolment

60

Participant exclusion criteria

1. Deterioration after IVIg withdrawal in the last 12 months
2. Changes in IVIg treatment dose/interval in last 6 months
3. Change of additional CIDP treatment, if any, in the last 3 months (e.g., corticosteroids or immunosuppressive treatment)
4. A prolonged period (> 6 weeks) of disability increase following an earlier IVIg withdrawal attempt
5. History of respiratory failure related to CIDP
6. Legally incompetent
7. Lack of written informed consent

Recruitment start date

01/04/2014

Recruitment end date

01/10/2016

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Centre
Amsterdam
1105 AZ
Netherlands

Organisation

Academic Medical Center Amsterdam (Netherlands)

Sponsor details

Department of Neurology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
-
i.n.vanschaik@amc.uva.nl

Sponsor type

Hospital/treatment centre

Website

http://www.amc.nl/web/Research/ResearchAMC/AMC-a-glance.htm

Funder type

Government

Funder name

ZonMw/Rational Pharmacotherapy programme (Netherlands) (Dutch Governmental grant)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Sanquin Blood Supply (Netherlands) (logistical support)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

01/01/2021

Individual participant data (IPD) sharing plan

The datasets with clinical data that do not include confidential patient information generated during and/or analysed during the current study will be available upon reasonable request from F. Eftimov (f.eftimov@amsterdamumc.nl) after publishing the results.

IPD sharing plan summary

Available on request

Study outputs