Primary objective of this randomized controlled trial is to assess whether combining IVIg and IVMP leads to more frequent long-term remission in CIDP compared to treatment with IVIg alone. Main secondary objectives are to assess whether IVIg and…
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the number of patients in remission at 1 year after start of
an 18 weeks treatment period. 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 I-RODS
and/or improvement of one or more points on the INCAT disability scale at 18
weeks compared to baseline. Sustained is defined as no deterioration between 18
weeks and 52 weeks, i.e. difference on the I-RODS of less than the individual
MCID difference and one or more points on the INCAT disability scale. Patients
will be considered as a treatment failure if they 1) receive additional CIDP
treatment during the 18-week intervention period, 2) do not improve at 18
weeks, 3) restart CIDP treatment for any reason between 18 and 52 weeks, or 4)
do not show a sustained improvement at 52 weeks as defined above.
Secondary outcome
Secondary parameters will be assessed at 18 and 52 weeks, or earlier if a
preliminary endpoint is reached. Secondary parameters include:
1) The number of patients with improvement on disability equal or more than the
MCID;
2) Time to improvement (>= MCID) on disability;
3) Mean change in disability;
4) Mean change in grip strength;
5) Mean change in muscle strength;
6) Mean change in sensory impairment;
7) Mean change in fatigue;
8) Mean change in pain;
9) Mean change in health related quality of life (HRQL);
10) Number of (serious) adverse events (including corticosteroid associated
adverse events);
11) Care use and overall healthcare-related costs.
Background summary
Induction treatment of CIDP currently consists of either intravenous
immunoglobulin (IVIg) infusions or high dose corticosteroids, including daily
oral prednisolone, pulsed dexamethasone or pulsed intravenous
methylprednisolone (IVMP). 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. Alternatively, corticosteroids probably
lead to longterm remissions. Both fast clinical response and long term
remissions can be considered equally important.
Study objective
Primary objective of this randomized controlled trial is to assess whether
combining IVIg and IVMP leads to more frequent long-term remission in CIDP
compared to treatment with IVIg alone. Main secondary objectives are to assess
whether IVIg and IVMP leads more often to functional improvement and a faster
rate of functional improvement compared to IVIg alone.
Study design
A multicenter, randomized, double-blind, placebo-controlled trial.
Intervention
Intravenous methylprednisolone (1 gram) or placebo (sodium chloride 0.9%, 100
ml). All patients receive (weekly) alendronic acid and (daily) calcium/vitamin
D during the 18-week intervention period according to national guidelines for
prevention of glucocorticoid-induced osteoporosis.
Study burden and risks
This study is considered of moderate risk. Side effects associated with
methylprednisolone are well documented and include hypertension, diabetes,
osteoporosis, Cushinoid appearance, gastrointestinal complaints and mood
changes. Total follow-up of the study is 104 weeks, including the final
safety-follow-up. Follow-up hospital visits will be scheduled at 6, 12, 18, 24,
52 and 104 weeks. Patients are contacted by phone at 3, 30 and 42 weeks after
start treatment to fill in a limited number of questionairres). Unscheduled
visits (including visits during relapses) can be scheduled at any time.
Meibergdreef 9
Amsterdam Zuid-Oost 1105 AZ
NL
Meibergdreef 9
Amsterdam Zuid-Oost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion of patients is based on the presence of active disease and
fulfillment of the probable or definite. EFNS/PNS criteria for CIDP. All new
and untreated adult patients are eligible for the study. In addition we will
include CIDP patients, treated previously, who have a disease relapse after a
remission of at least 1 year, and patients who have responded to their first
course of IVIg in the last three months but deteriorated afterwards.
Deterioration after treatment is defined as any deterioration warranting
treatment as judged by the treating physician.
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), with the exception
of low dose prednisone (20 mg or less for the 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 less than 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002511-34-NL |
| ISRCTN | ISRCTN15893334 |
| CCMO | NL62561.018.17 |