Clinical trial NCT03542279: CPI Combination Therapy for Autoimmune Encephalitis
Official title: Combination Therapy of Pulse Corticosteroid and Plasma Exchange Followed by Intravenous Immunoglobulin in Patients With Severe Antibody- Associated Autoimmune Encephalitis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autoimmune Encephalitis
Keywords: Autoimmune encephalitis, Plasma exchange, Immunotherapy, Outcome
corticosteroid
immunoglobulin
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2018-05-31
Enrollment: 70
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Corticosteroids, intravenous immunoglobulin (IVIG), and plasma exchange (PE) are the first-line therapies for autoimmune encephalitis (AE) patients, but optimal first-line treatment strategy for different AE patients remains undetermined. The study is to compare the efficacy between pulse corticosteroid plus PE initially followed by IVIG (CPI therapy) and pulse corticosteroid plus IVIG followed by PE two weeks later (CIP therapy) in patients with severe antibody-associated autoimmune encephalitis (AE).

Detailed description: Patients with AE will be randomly divided into the CPI and CIP group according to the random table. All patients will receive tumour screening, symptomatic supportive treatment, and immunotherapy. The immunotherapy includes intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG; 0.4 g/kg/d for each course for 5 d), PE and immunosuppressants. Patients in the CPI group received IVMP and PE treatment without delay, followed by IVIG immediately after PE treatment. Patients in the CIP group were given IVMP and IVIG and IVMP immediately, followed by PE at least 2 weeks after IVIG treatment. The patients received long-term immunotherapy involving a combination of oral corticosteroids and immunosuppressants (such as mycophenolate mofetil at a dose of 1-2g/d) for 6-12 months if no contraindications. The primary outcome is the proportion of patients achieving functional improvement \[a decrease of at least 1 point in modified Rankin Scale (mRS) score\] at 3 months after immunotherapy.

Eligibility criteria: Inclusion criteria:

1. 14-65 years old;
2. met all the three following diagnostic criteria of AE: (i) subacute onset (rapid progress of less than 3 months) of working memory deficits, altered mental status, or psychiatric symptoms; (ii) at least one of the followings: new focal CNS findings, seizures not explained by a previously known disease, cerebrospinal fluid (CSF) pleocytosis (white blood cell count 5 cells/mm3), magnetic resonance imaging (MRI) features suggestive of encephalitis, and (iii) reasonable exclusion of alternative causes;
3. the presence of antibody in serum or CSF indicating a positive diagnosis of AE using a cell-based assay;
4. critically ill with a modified Rankin scale (mRS) score of 4 to 5;
5. within 3 months of onset;
6. no immunotherapy previously.

Exclusion criteria:

1. relative contraindications of TPE treatment: serious underlying diseases such as severe active hemorrhage, disseminated intravascular coagulation, severe hypotension or shock, unstable cardiac failure, cerebral herniation, severe infection or other endangered conditions;
2. allergic to immunoglobulin;
3. contraindications of glucocorticoid therapy: glucocorticoid allergy, active gastric or duodenal ulcer, severe osteoporosis, diabetes, hypertension after recent gastrointestinal anastomosis, and serious infection that cannot be controlled by antibiotics;
4. serious underlying diseases, such as cardiac dysfunction, arrhythmia, and coagulation disorders;
5. premorbid mRS ≥ 3.

Primary outcomes:
measure: proportion of subjects achieving functional improvement
timeFrame: 3 months following Immunotherapy
Secondary outcomes:
measure: modified Rankin Scale
timeFrame: 3 months following Immunotherapy
measure: modified Rankin Scale
timeFrame: 6 months following Immunotherapy
measure: modified Rankin Scale
timeFrame: 12 months following Immunotherapy
measure: modified Rankin Scale
timeFrame: 24 months following Immunotherapy
measure: proportion of favorable outcome
timeFrame: 3 months following Immunotherapy
measure: proportion of favorable outcome
timeFrame: 6 months following Immunotherapy
measure: proportion of favorable outcome
timeFrame: 12 months following Immunotherapy
measure: proportion of favorable outcome
timeFrame: 24 months following Immunotherapy
measure: CASE score
timeFrame: 3 months following Immunotherapy
measure: CASE score
timeFrame: 6 months following Immunotherapy
measure: CASE score
timeFrame: 12 months following Immunotherapy
measure: CASE score
timeFrame: 24 months following Immunotherapy
measure: Length of ICU stay
timeFrame: before discharge
Other outcomes:
measure: Adverse events
timeFrame: within 24 months following immunotherapy
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital of Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Yan Zhang, MD, Phd
role: STUDY_CHAIR
References: