CPI Combination Therapy for Autoimmune Encephalitis

NCT ID: NCT03542279

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-25
• Study Completion Date: 2024-09-12

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.

Conditions

Autoimmune Encephalitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

CPI group

Intravenous methylprednisolone (IVMP) combined with PE (5 times in each course) and IVIG after PE.

Group Type: EXPERIMENTAL

Plasma exchange (PE)

Intervention Type: PROCEDURE

PE is performed every other day using a multi-filtrate apheresis device (Fresenius, Bad Homburg, Germany), and 5 times in total for each course. The plasma removed during PE is replaced with an equal volume of substitution (half 5% albumin with normal saline and half plasma). The plasma volume to be replaced was estimated according to the following formula: plasma volume (L) = 7.5%×weight (kg)×(1-hematocrit)×1000ml. Heparin was added to the exchange circuit to prevent blood clotting. The exchange rate was monitored, recorded, and balanced to prevent cardiovascular instability. Blood pressure and other vital signs were closely monitored every 15 minutes throughout the exchange.

intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)

Intervention Type: DRUG

IVIG is given 0.4 g/kg/d for each course for 5 days. IVMP is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.

CIP group

IVMP and IVIG (0.4g/kg/d for 5 days) immediately, followed by PE at least 2 weeks after IVIG treatment.

Group Type: ACTIVE_COMPARATOR

Plasma exchange (PE)

Intervention Type: PROCEDURE

PE is performed every other day using a multi-filtrate apheresis device (Fresenius, Bad Homburg, Germany), and 5 times in total for each course. The plasma removed during PE is replaced with an equal volume of substitution (half 5% albumin with normal saline and half plasma). The plasma volume to be replaced was estimated according to the following formula: plasma volume (L) = 7.5%×weight (kg)×(1-hematocrit)×1000ml. Heparin was added to the exchange circuit to prevent blood clotting. The exchange rate was monitored, recorded, and balanced to prevent cardiovascular instability. Blood pressure and other vital signs were closely monitored every 15 minutes throughout the exchange.

intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)

Intervention Type: DRUG

IVIG is given 0.4 g/kg/d for each course for 5 days. IVMP is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.

Interventions

Plasma exchange (PE)

PE is performed every other day using a multi-filtrate apheresis device (Fresenius, Bad Homburg, Germany), and 5 times in total for each course. The plasma removed during PE is replaced with an equal volume of substitution (half 5% albumin with normal saline and half plasma). The plasma volume to be replaced was estimated according to the following formula: plasma volume (L) = 7.5%×weight (kg)×(1-hematocrit)×1000ml. Heparin was added to the exchange circuit to prevent blood clotting. The exchange rate was monitored, recorded, and balanced to prevent cardiovascular instability. Blood pressure and other vital signs were closely monitored every 15 minutes throughout the exchange.

Intervention Type: PROCEDURE

intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)

IVIG is given 0.4 g/kg/d for each course for 5 days. IVMP is 1,000 mg or 500 mg methylprednisolone for 3 or 5 days, and the dosage of glucocorticoid will gradually decrease.

Intervention Type: DRUG

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 against neuronal surface antigen 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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Yan Zhang

Chief physician, professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yan Zhang, MD, Phd

Role: STUDY_CHAIR

Xuanwu Hospital, Beijing

Locations

Xuanwu Hospital of Capital Medical University

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

AE-CPI

Identifier Type: -

Identifier Source: org_study_id