|- candidate number||13994|
|- NTR Number||NTR3705|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||14-nov-2012|
|- Secondary IDs|| |
|- Public Title||Dose response of IVIg in CIDP.|
|- Scientific Title||Dose response trial of IV immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. |
|- hypothesis||The main objective is to investigate whether high frequency low dosage IVIg treatment is more effective than low frequency high dosage as maintenance treatment for CIDP. The secondary objective is to investigate whether high frequency low dosage of IVIg results in less adverse events compared to low frequency high dosage. |
|- Healt Condition(s) or Problem(s) studied||Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIPD), Immunoglobulin|
|- Inclusion criteria||1. Diagnosis of CIDP or acute-onset CIDP made by a consultant neurologist, fulfilling the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical diagnostic criteria;|
2. Age 18 years or older;
3. Significant improvement following the first use of IVIg, defined as a decrease of ≥ 1 grade on the modified Rankin disability scale;
4. To indicate that the patient is still IVIg dependent and has active CIDP, he/she must have shown an objective deterioration (decrease in muscle strength measured with the vigorimeter and/or MRC sum score following reduction of IVIg dose at some time during the 6 months before randomisation;
5. Ongoing intermittent treatment with 10% liquid IVIg (Kiovig) for at least 3 months. The dose must have been not changed within the 8 weeks prior to the study;
6. EMG findings compatible with CIDP showing peripheral nerve demyelination at least once during their illness;
7. Signed informed consent by the patient.
|- Exclusion criteria||1. Known IgA deficiency or known allergic reaction to IVIg.|
2. Hand grip strength measured by the Martin Vigorimeter equal or more than the median value (kPa) for an age and sex matched healthy control;
3. Maintenance dose less than 15 gram of IVIg every infusion or an infusion interval less than 14 days;
4. Known hereditary neuropathy or severe concomitant diseases such as HIV infection, Lyme disease, chronic active hepatitis, congestive heart failure, systemic lupus erythematosus, drug or toxin induced neuropathy, vasculitis, and malignancies;
5. Multifocal motor neuropathy (MMN), fulfilling the European Federation of Neurological Societies /Peripheral Nerve Society criteria;
6. IgM paraprotein with anti-myelin-associated glycoprotein (MAG) antibodies;
7. Atypical CIDP with pure sensory or persistent unifocal impairment or significant central nervous system involvement;
8. Participation in a controlled trial of an investigational medicinal product within the past 12 weeks;
9. Severe known abnormalities in liver, kidney function or serum glucose level;
10. Treatment with more than 20 milligrams of prednisone a day;
11. Treatment with other immunosuppressives (e.g. methotrexate, azathioprine, prednisone) if the dosage has been changed within 8 weeks prior to start of the study.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2013|
|- planned closingdate||1-mei-2014|
|- Target number of participants||17|
|- Interventions||Intervention group/arm:|
4 infusions of IVIg of half the normal dosage (with placebo added to maintain the total volume) and half the interval (double the frequency).
2 infusion of IVIg according to the normal; dose and interval as well as two sham (placebo) infusions.
The total amount of IVIg given during the whole double-blind phase will remain the same in both groups. As this is a crossover study all pateints will receive both treatment schedules once.
|- Primary outcome||Hand grip strength (Vigorimeter) will be used as the primary outcome
measure. A difference in the (mean of the 4) Vigorimeter changes from
baseline between the two groups of > 8 kPa (mean of both hands) is
considered clinically relevant. A difference of > 8 kPa in Vigorimeter
change from baseline in favour of the group treated with half the dosage
and interval as compared with the other treatment group will be
considered a clinical relevant improvement. |
|- Secondary outcome||The Rasch-built overall disability scale (R-ODS) measuring activity status, Rasch fatigue severity scale (R-FSS) measuring fatigue, and quality of life (SF-36) will be used as secondary
outcome measures. The secondary objective will be to record the
occurrence of side-effects. |
|- Timepoints||The study period will be approximately 14-26 weeks, depending on infusion frequency prior to randomisation and includes two “wash-out” infusions. Prior to every infusion, muscle grip strength (Vigorimeter) will be measured (mean of three measurements of both hands) by the nurse. The R-ODS, R-FSS and SF-36 questionnaires will be completed by the patient just before every IVIg infusion.|
AEs will be reported by the nurse during every infusion. Just after every infusion a side-effect questionnaire will be completed by the patient.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| Krista Kuitwaard|
|- CONTACT for SCIENTIFIC QUERIES||Prof. P.A. Doorn, van|
|- Sponsor/Initiator ||Erasmus Medical Center, Rotterdam|
(Source(s) of Monetary or Material Support)
|Baxter Healthcare Corporation|
|- Brief summary||Rationale: |
High peak levels of serum IgG may not be needed for maintenance treatment of CIDP with intravenous immunoglobulin (IVIg). More frequent dosing of IVIg leads to more stable IgG levels and higher trough levels which appear to correspond with clinical efficacy. Furthermore more frequent dosing leads to lower peak levels which when high are responsible for the systemic side-effects.
The main objective is to investigate whether high frequency low dosage IVIg treatment is more effective than low frequency high dosage as maintenance treatment for CIDP. The secondary objective is to investigate whether high frequency low dosage of IVIg results in less adverse events compared to low frequency high dosage.
Double-blind randomised controlled cross-over intervention study.
Chronic inflammatory demyelinating polyneuropathy (CIDP) patients who are IVIg dependent receiving a stable maintenance dose and interval of IVIg (Kiovig).
One group will be treated with half their normal dosage of IVIg (with placebo added to maintain the total volume) at half their interval (double their frequency). The other group will be treated with their normal dosage and interval of IVIg followed by a placebo (albumin) infusion. After a wash-out phase, patients will cross-over to the other treatment group.
Main study parameters/endpoints:
Hand grip strength (Vigorimeter) will be used as the primary outcome measure. A difference of > 8 kPa in the mean of the 4 Vigorimeter changes from baseline in favour of the group treated with half the dosage and interval as compared with the other group will be considered a clinical relevant improvement. Changes in the R-ODS, R-FSS, and SF-36 and the occurrence of side-effects will be used as secondary outcome measures.
|- Main changes (audit trail)|
|- RECORD||14-nov-2012 - 25-nov-2012|