CPI Combination Therapy for Autoimmune Encephalitis

NCT03542279 | Completed

• 1 other identifier: AE-CPI
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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).

Conditions

Autoimmune Encephalitis

Keywords

Autoimmune encephalitis, Plasma exchange, Immunotherapy, Outcome; corticosteroid; immunoglobulin

Outcome Measures

Primary Outcomes (1)

• proportion of subjects achieving functional improvement

  Functional improvement is defined as a decrease of at least 1 point in mRS score, modified Rankin Scale: 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

  3 months following Immunotherapy

Secondary Outcomes (13)

• modified Rankin Scale

  3 months following Immunotherapy

• modified Rankin Scale

  6 months following Immunotherapy

• modified Rankin Scale

  12 months following Immunotherapy

• modified Rankin Scale

  24 months following Immunotherapy

• proportion of favorable outcome

  3 months following Immunotherapy

Other Outcomes (1)

• Adverse events

  within 24 months following immunotherapy

Study Arms (2)

CPI group

EXPERIMENTAL

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

Procedure: Plasma exchange (PE); Drug: intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)

CIP group

ACTIVE COMPARATOR

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

Procedure: Plasma exchange (PE); Drug: intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP)

Interventions

Plasma exchange (PE) 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.

CIP group; CPI group

intravenous immunmoglobulin (IVIG), intravenous methylprednisolone (IVMP) 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; CPI group

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years old;
• the presence of antibody against neuronal surface antigen in serum or CSF indicating a positive diagnosis of AE using a cell-based assay;
• critically ill with a modified Rankin scale (mRS) score of 4 to 5;
• within 3 months of onset;
• no immunotherapy previously.

You may not qualify if:

• 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;
• allergic to immunoglobulin;
• 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;
• serious underlying diseases, such as cardiac dysfunction, arrhythmia, and coagulation disorders;
• premorbid mRS ≥ 3.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Xuanwu Hospital of Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

MeSH Terms

Conditions

Autoimmune Diseases of the Nervous System

Interventions

Plasma Exchange; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yan Zhang, MD, Phd

  Xuanwu Hospital, Beijing

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, professor

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: May 31, 2018
• Study Start: November 25, 2020
• Primary Completion: December 12, 2022
• Study Completion: September 12, 2024
• Last Updated: June 27, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)