Condition category
Nervous System Diseases
Date applied
26/01/2018
Date assigned
12/02/2018
Last edited
30/05/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder which causes chronic inflammation (swelling) of nerves causing weakness and sensory problems in legs and arms. Induction treatment (the first phase of treatment) CIDP currently consists of either intravenous immunoglobulin (IVIg) (treatment made from donated blood that contains health anitbodies) infusions or high dose corticosteroids (anti-inflammatory medication), including daily oral prednisolone, pulsed dexamethasone or pulsed intravenous methylprednisolone (IVMP) (types of steroids). Both IVIg and IVMP are recommended as first line treatment, but choice of induction treatment is usually based on patients' and physicians' preferences as both treatment options have their own specific advantages. Patients treated with IVIg usually respond fast, but this treatment rarely leads to long term remissions (meaning the symptoms are gone). Corticosteroids may lead to long term remissions. Both fast clinical response and long term remissions can be considered equally important. The aim of this study is to determine whether the addition of methylprednisolone to IVIg as induction treatment leads to a better outcome.

Who can participate?
Adults aged 18 and older who have probably or definite CIDP.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive intravenous immunoglobulin (IVIg) + intravenous methylprednisolone. Those in the second group receive intravenous immunoglobulin (IVIg) + placebo (saline infusion). Participants receive seven infusions every three weeks over the course of 18 weeks. During the 18 week intervention period participants are prescribed osteoporosis prophylactics (vitamin D daily and alendronic acid weekly). In the Netherlands the first treatment is given in the hospital and the remaining six infusions are given at home. Outpatient clinic visits are planned every six weeks during the intervention period and a consultation by phone is planned three weeks after start of intervention period. Three follow-up visits are planned in week 24, 52 and 104. Unscheduled visits can be planned at any time during study.

What are the possible benefits and risks of participating?
Participants can benefit from the combination therapy: a fast improvement of symptoms(attributed to the IVIg) and long term remission (attributed to the methylprednisolone), without the need for further treatments. Risks include medication induced side effects. These side effects include (and not limited to) gastro-intestinal complaints, headaches, muscle aches, oedema, mood/behavior disorders (methylprednisolone); musculoskeletal complaints (muscle, joint and/or bone aches) and gastro-intestinal complaints (alendronic acid); skin rash, hypertension, headaches and gasto-intestinal complaints (IVIg, standard care).

Where is the study run from?
This study is being run by the Academic Medical Center (AMC) (The Netherlands). A total of 14 hospitals (8 in The Netherlands and 6 in the United Kingdom) are participating in this trial.

When is the study starting and how long is it expected to run for?
January 2018 to December 2023

Who is funding the study?
The Academic Medical Center (AMC) (The Netherlands)

Who is the main contact?
Dr Filip Eftimov (Scientific)
f.eftimov@amc.nl
2. Mr Sander Bus (Public)
s.r.bus@amc.nl

Trial website

Contact information

Type

Scientific

Primary contact

Dr Filip Eftimov

ORCID ID

http://orcid.org/0000-0002-0146-0776

Contact details

Academic Medical Center
Department of Neurology
PO Box 22660
Amsterdam
1100 DD
Netherlands
+31 20 566 8728
f.eftimov@amc.nl

Type

Public

Additional contact

Mr Sander Bus

ORCID ID

Contact details

Academic Medical Center
Department of neurology
H2-235
PO Box 22660
Amsterdam
1100DD
Netherlands
+31 20 566 6889
s.r.bus@amc.nl

Additional identifiers

EudraCT number

2017-002511-34

ClinicalTrials.gov number

Protocol/serial number

Protocol version 1.0 (26NOV2017); ABR: NL 62561.018.17

Study information

Scientific title

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in CIDP

Acronym

OPTIC

Study hypothesis

Primary objective of this randomized controlled trial is to assess whether combining IVIg and methylprednisolone leads to more frequent long-term remission in CIDP compared to treatment with IVIg alone.

Ethics approval

The Medical Ethical Committee of the Academic Medical Center, 15/01/2018, ref: 2017_316

Study design

Multicentre randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Intervention

All participants are treated with intravenous IVIg, which is considered standard care. In addition, participants are randomized to receive either 7 infusions methylprednisolone (IVMP) 1000 mg in sodium chloride 0,9%, or placebo (100 ml sodium chloride 0,9%). Participants are treated every 3 weeks during an 18-week intervention period. In addition, all patients receive osteoporosis prophylactics (calcium/vitamin D 500 mg/800IE daily and alendronic acid 80 mg weekly) during the 18 week intervention period.

In the Netherlands the first treatment is given in the hospital and the remaining six infusions are given at home. Outpatient clinic visits are planned every 6 weeks during the intervention period and a consultation by phone is planned 3 weeks after start of intervention period. Three follow-up visits are planned in week 24, 52 and 104. Unscheduled visits can be planned at any time during study. A total of 14 hospitals (8 in The Netherlands and 6 in the United Kingdom) are participating in this trial. The Academic Medical Center (AMC) in Amsterdam (The Netherlands) is the study sponsor.

Intervention type

Drug

Phase

Phase III

Drug names

IVIg (standard care)
Methylprednisolone (intervention)
Sodium chloride 0.9% (placebo)
Calcium/vitamin D (osteoporosis prophylactic)
Alendronic acid (osteoporosis prophylactic)

Primary outcome measure

The number of patients in remission is a value determined 1 year after start of the intervention period by accounting for the patients who fit the criteria for remission. Remission is defined as: sustained improvement without the need for further treatment. Improvement is defined as improvement by at least the minimal clinical important difference (MCID) on the inflammatory Rasch Disability Scale (I-RODS) and/or improvement (ie, decrease) of one point or more on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale at 18 weeks compared to baseline. Sustained is defined as no deterioration between week 18 and week 52, i.e. difference on the I-RODS of less than the individual MCID difference and/or no increase on the adjusted INCAT disability scale.

Secondary outcome measures

Secondary parameters are assessed at 18 and 52 weeks, or earlier if a preliminary endpoint is reached:
1. The number of patients with improvement on disability equal or more than the MCID: disability is measured using the iRODS and the INCAT disability scale, the number of patients are calculated by counting the patients who fit the definition of improvement
2. Time to improvement (≥ MCID) on disability: time to improvement is calculated and given in days and/or weeks
3. Mean change in disability: disability is measured using the iRODS and INCAT disability scale
4. Mean change in grip strength: grip strength (in kPa) is measured using a handheld (Martin) Vigorimeter
5. Mean change in muscle strength: The Medical Research Council (MRC) sum score of 12 predefined muscle groups (including shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and foot dorsiflexion) is used to measure muscle strength
6. Mean change in sensory impairment: measured using the Inflammatory Neuropathy Cause and Treatment sensory sumscore (INCAT-SS)
7. Mean change in fatigue: measured using the Fatigue Severity Scale (FSS)
8. Mean change in pain: measured using the pain intensity numeric rating scale (PI-NRS)
9. Mean change in health related quality of life (HRQL): measured using the EuroQol
10. Number of (serious) adverse events (including corticosteroid associated adverse events): number of (serious) adverse events (including corticosteroid associated adverse events) are measured using a structured questionnaire with short term corticosteroid and IVIg related AE’s at the 18 week visit. AEs are scored as mild, moderate or severe by the investigator. Long-term corticosteroid related AEs will be filled in by the investigator at 52 weeks (secondary outcome) and 104 weeks (safety follow-up). Adverse events questionnaires will be filled in only after completion of all other outcome assessments.
11. Care use and overall healthcare-related costs: measured using the working documents and the Medical Consumption Questionnaire (iMCQ) complemented with extra questions relevant for the study population and the Productivity Cost Questionnaire (iPCQ)

Overall trial start date

01/01/2018

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Probable or definite CIDP according to the EFNS/PNS criteria 2010 (all CIDP phenotypes)
2. Age ≥ 18 years
3.1. Treatment naïve patients; or
3.2. Previously treated patients who have a relapse after a remission of at least 1 year; or
3.3. Patients treated with subjective or objective improvement after a single loading dose of IVIg in the last 3 months, and subsequent deterioration as judged by his or her treating physician.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

96

Participant exclusion criteria

Current exclusion criteria as of 30/05/2018, to reflect changes approved by ethics committee 25/05/2018:
1. Presence of IgM paraproteinemia and/or anti-MAG antibodies or CIDP specific antibodies associated with poor treatment response to IVIg
2. Use of drugs associated with a demyelinating neuropathy
3. Use of any immunosuppressive or immunomodulatory drugs in previous 6 months (except for a single loading dose of IVIg within 3 months or low dose prednisolone (20 mg or less) during a short period (maximum duration of two weeks).
4. Known serious adverse events with previous IVIg or corticosteroid treatment
5. One of more of the risk factors associated with increased risk of adverse events of IVIg or IVMP or conditions that could lead to unblinding of treatment (i.e. diabetes; IgA deficiency; gastric ulcers; psychosis; severe hypertension (180/110 mmHg or more on repeated measurements); hypocalcaemia (lower than 2.20 mmol/L, corrected for albumin); moderate or severe heart failure; severe cardiovascular disease (i.e. more than one myocardial infarction and or ischemic stroke); renal failure (glomerulal filtratrion rate < 30 ml/min)
6. History of osteoporosis or osteoporotic fractures
7. Known malignancy with survival expectancy of less than 1 year
8. Bodyweight more than 120 kg
9. Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study
10. Cataract
11. Psychosis
12. Poor dental status
13. Known pulmonary embolism or other deep venous thrombosis in patient’s medical history, without current anticoagulant therapy
14. Legally incompetent adults
15. Lack of written informed consent

Previous exclusion criteria:
1. Presence of IgM paraproteinemia and/or anti-MAG antibodies or CIDP specific antibodies associated with poor treatment response to IVIg
2. Use of drugs associated with a demyelinating neuropathy
3. Use of any immunosuppressive or immunomodulatory drugs in previous 6 months (except for a single loading dose of IVIg within 3 months or low dose prednisolone (20 mg or less) during a short period (maximum duration of two weeks).
4. Known serious adverse events with previous IVIg or corticosteroid treatment
5. One of more of the risk factors associated with increased risk of adverse events of IVIg or IVMP or conditions that could lead to unblinding of treatment (i.e. diabetes; IgA deficiency; gastric ulcers; psychosis; severe hypertension (180/110 mmHg or more on repeated measurements); hypocalcaemia (lower than 2.20 mmol/L, corrected for albumin); moderate or severe heart failure; severe cardiovascular disease (i.e. more than one myocardial infarction and or ischemic stroke); renal failure (glomerulal filtratrion rate < 30 ml/min)
6. History of osteoporosis or osteoporotic fractures
7. Known malignancy with survival expectancy of less than 1 year
8. Bodyweight more than 120 kg
9. Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study
10. Cataract
11. Psychosis
12. Poor dental status
13. Legally incompetent adults
14. Lack of written informed consent

Recruitment start date

01/02/2018

Recruitment end date

01/11/2020

Locations

Countries of recruitment

Netherlands, United Kingdom

Trial participating centre

Academic Medical Center (AMC)
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Trial participating centre

Erasmus Medical Center
Rotterdam
3015 CE
Netherlands

Trial participating centre

University Medical Center Utrecht
Utrecht
3584 CX
Netherlands

Trial participating centre

Maastricht University Medical Center
Maastricht
6229 HX
Netherlands

Trial participating centre

Radboud University Medical Center
Nijmegen
6525 GA
Netherlands

Trial participating centre

HaGa Hospital
The Hague
2545 AA
Netherlands

Trial participating centre

Martini Hospital Groningen
Groningen
9728 NT
Netherlands

Trial participating centre

Catharina Hospital Eindhoven
Eindhoven
5623 EJ
Netherlands

Trial participating centre

University College London Hospital
London
London NW1 2BU
United Kingdom

Trial participating centre

King's College Hospital
London
SE5 9RS
United Kingdom

Trial participating centre

University Hospitals of Birmingham
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Queen Elizabeth University Hospital
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

The Walton Centre
Liverpool
L9 7LJ
United Kingdom

Sponsor information

Organisation

Academic Medical Center (AMC)

Sponsor details

Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

ZonMw

Alternative name(s)

Netherlands Organisation for Health Research and Development

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

Netherlands

Funder name

Prinses Beatrix Spierfonds

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Sanquin Plasma Products B.V.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal, with the intent to publish the results in one year following overall trial end date.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date. When this information becomes available we will disclose it.

Intention to publish date

31/12/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

30/05/2018: The participant exclusion criteria have been changed.