Intravenous immunoglobulin overtreatment in chronic inflammatory demyelinating polyneuropathy
| ISRCTN | ISRCTN13637698 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13637698 |
| EudraCT/CTIS number | 2013-005363-52 |
| Secondary identifying numbers | IOC |
- Submission date
- 06/12/2013
- Registration date
- 25/03/2014
- Last edited
- 01/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
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 participants 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
Contact information
Scientific
Academic Medical Centre
Department of Neurology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| f.eftimov@amc.uva.nl |
Study information
| 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 |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Intravenous immunoglobulin overtreatment in chronic inflammatory demyelinating polyneuropathy: a randomized controlled non-inferiority trial |
| Study 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 |
| 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 (INCATSS, range 0-20). 5. Subjects 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 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 |
| Total final enrolment | 60 |
| 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 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 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
1105 AZ
Netherlands
Sponsor information
Hospital/treatment centre
Department of Neurology
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| i.n.vanschaik@amc.uva.nl | |
| Website | http://www.amc.nl/web/Research/ResearchAMC/AMC-a-glance.htm |
Funders
Funder type
Government
No information available
No information available
Results and Publications
| Intention to publish date | 01/01/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 03/06/2022 | 01/11/2022 | Yes | No |
Editorial Notes
01/11/2022: Publication reference and total final enrolment added.
01/10/2020: Intention to publish date added.
12/09/2019: IPD sharing statement added.
29/01/2019: The overall trial end date has been changed from 01/10/2016 to 31/07/2019
