Ignite Creation Date:
2024-05-06 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 12:49 PM
Study NCT ID:
NCT03586557
Status:
UNKNOWN
Last Update Posted:
2021-08-17
First Post:
2018-06-13
Brief Title:
Effectiveness of Plasma Exchange in Treating With Severe Acute AQP4-Ab Positive Optic Neuritis
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
Effectiveness of Plasma Exchange in Treating With Severe Acute AQP4-Ab Positive Optic Neuritis
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients aged between 18 and 70 with acute aquaporin-4 immunoglobulin G antibodies AQP4-IgG positive optic neuritis irrespective of prior using of corticosteroids in this episode of disease are chosen by the physician Patients will then be randomized to receive high dose of intravenous corticosteroids combined with plasma exchange PE or merely high dose of intravenous corticosteroids followed subsequent taper The main outcome of visual acuity and OCT parameters will be compared at baseline one three and six months after treatments and other assessments will also be recorded and compared This will allow for determination on whether additional PE plays a role in better prognosis in acute AQP4-IgG positive optic neuritis
Detailed Description:
Definition
This will be a parallel designed open-labeled randomized add-on comparison study between 1 intravenous high dose corticosteroids combined with plasma exchange PE and 2 merely intravenous high dose corticosteroids followed subsequent taper of the improvement of optic nerve function in acute aquaporin-4 immunoglobulin G antibodies AQP4-IgG positive optic neuritis The investigators will compare assessments at baseline with those at one three and six months post treatments
Patients
Subjects will be recruited from in-patients who were diagnosed as AQP4-IgG positive optic neuritis in Neuro-Ophthalmology Department in Peoples Liberation of Army General Hospital PLAGH in Beijing China
Eligible participants should have inaugural or recurrent unilateral or bilateral optic neuritis attacks within 30 days from the first symptom onset Only affected eyes with VA less than 20200 at baseline will be included in the study All of the participants have to have positive serum AQP4-IgG Enrollment will be allowed irrespective of whether a previous diagnosis of neuromyelitis optica spectrum disorders NMOSD was made
Participants will be randomly assigned 11 to exclusively intravenous corticosteroid CS group or sequential intravenous corticosteroid and PE CS and PE group
All participants will receive intravenous corticosteroid 1g of methylprednisolone per day for 35days and subsequent taper The treatment will be started as soon as the participant is admitted to the hospital The participants in CS and PE group will receive add-on five consecutive PE every other day performed in the ward
Primary and secondary endpoints
The primary endpoint will be the value of visual acuity VA at end of follow-up 6 months in the affected eyes VA was assessed separately for each eye using Snellens test chart at baseline one three and six months and was converted to LogMAR for calculation of the mean visual acuity If the patient has a relapse during the follow-up the last VA recorded before the relapse will be the final VA outcome of the patient
Optical Coherence Tomography OCT parameters assessed at months 6 will be another primary endpoint OCT will be performed with spectrum domain OCT SD-OCT Carl Zeiss 5000 Peripapillary retinal nerve fiber layer pRNFL macular retinal thickness and macular Ganglion Cell Layer inner plexiform layer mGCIPL will be measured by one skilled technician at the condition of dilated pupil to avoid bias of measurement Parameters above will be recorded thereafter
Secondary endpoints will study the numbers of relapses during the follow-up of 6 months optic nerve conduction velocity measured by Flash Visual Evoked Potential FVEP at the end of follow-up 6 months FVEP will be recorded by visual electro-physiology equipment Roland RETI-PortScan 21 The same technician will perform all the assessments for all the patients to avoid bias of measurement A final latency assessment was analysed at study end
Titer of serum AQP4-IgG within 1 month after their attack and six months after treatment will be recorded Orbital MRI will be assessed and compared if it is necessary
Security indexes
Safety assessment at screeningbaselineone three and six month are physical examination and vital signs including blood pressure BP heart rate HR Hematology and blood chemistry will be assessed as well blood routine test coagulation Test and serum electrolyte will be tested during the PE treatment and followed up at one three and six months Allergies during PE treatment will be recorded by doctors Patients experiencing severe adverse events would be remove from the treatment arm However patients with slight or medium adverse events should complete their PE treatment unless they require to quit
Sample size
The estimated mean VA outcome of AQP4-IgG positive optic neuritis 6 months after its attack is expected to be about 14 LogMAR with its standard deviation SD around 13 LogMAR based on 2 observation reports Another observational study found that mean VA outcome after PE combined corticosteroid treated AQP4-IgG positive optic neuritis was 075 LogMAR The investigators assume that to achieve 80 power at 5 significance level using a parallel design the sample size needs to be 64 cases per group and 128 in all By accounting for 10 patients potentially withdrawing consent or being lost to follow-up over the course of the study the final sample size will be increased to 71 cases per arm and 142 patients in all
Planned Statistical Analysis
The primary analysis will be intention-to-treat The outcome of the superiority clinical trial will be assessed based on a two-sided 95 confidence interval around the mean VA and OCT outcome showing a credible range for true difference between merely corticosteroid and corticosteroid combined PE treatment
This will be a parallel designed open-labeled randomized add-on comparison study between 1 intravenous high dose corticosteroids combined with plasma exchange PE and 2 merely intravenous high dose corticosteroids followed subsequent taper of the improvement of optic nerve function in acute aquaporin-4 immunoglobulin G antibodies AQP4-IgG positive optic neuritis The investigators will compare assessments at baseline with those at one three and six months post treatments
Patients
Subjects will be recruited from in-patients who were diagnosed as AQP4-IgG positive optic neuritis in Neuro-Ophthalmology Department in Peoples Liberation of Army General Hospital PLAGH in Beijing China
Eligible participants should have inaugural or recurrent unilateral or bilateral optic neuritis attacks within 30 days from the first symptom onset Only affected eyes with VA less than 20200 at baseline will be included in the study All of the participants have to have positive serum AQP4-IgG Enrollment will be allowed irrespective of whether a previous diagnosis of neuromyelitis optica spectrum disorders NMOSD was made
Participants will be randomly assigned 11 to exclusively intravenous corticosteroid CS group or sequential intravenous corticosteroid and PE CS and PE group
All participants will receive intravenous corticosteroid 1g of methylprednisolone per day for 35days and subsequent taper The treatment will be started as soon as the participant is admitted to the hospital The participants in CS and PE group will receive add-on five consecutive PE every other day performed in the ward
Primary and secondary endpoints
The primary endpoint will be the value of visual acuity VA at end of follow-up 6 months in the affected eyes VA was assessed separately for each eye using Snellens test chart at baseline one three and six months and was converted to LogMAR for calculation of the mean visual acuity If the patient has a relapse during the follow-up the last VA recorded before the relapse will be the final VA outcome of the patient
Optical Coherence Tomography OCT parameters assessed at months 6 will be another primary endpoint OCT will be performed with spectrum domain OCT SD-OCT Carl Zeiss 5000 Peripapillary retinal nerve fiber layer pRNFL macular retinal thickness and macular Ganglion Cell Layer inner plexiform layer mGCIPL will be measured by one skilled technician at the condition of dilated pupil to avoid bias of measurement Parameters above will be recorded thereafter
Secondary endpoints will study the numbers of relapses during the follow-up of 6 months optic nerve conduction velocity measured by Flash Visual Evoked Potential FVEP at the end of follow-up 6 months FVEP will be recorded by visual electro-physiology equipment Roland RETI-PortScan 21 The same technician will perform all the assessments for all the patients to avoid bias of measurement A final latency assessment was analysed at study end
Titer of serum AQP4-IgG within 1 month after their attack and six months after treatment will be recorded Orbital MRI will be assessed and compared if it is necessary
Security indexes
Safety assessment at screeningbaselineone three and six month are physical examination and vital signs including blood pressure BP heart rate HR Hematology and blood chemistry will be assessed as well blood routine test coagulation Test and serum electrolyte will be tested during the PE treatment and followed up at one three and six months Allergies during PE treatment will be recorded by doctors Patients experiencing severe adverse events would be remove from the treatment arm However patients with slight or medium adverse events should complete their PE treatment unless they require to quit
Sample size
The estimated mean VA outcome of AQP4-IgG positive optic neuritis 6 months after its attack is expected to be about 14 LogMAR with its standard deviation SD around 13 LogMAR based on 2 observation reports Another observational study found that mean VA outcome after PE combined corticosteroid treated AQP4-IgG positive optic neuritis was 075 LogMAR The investigators assume that to achieve 80 power at 5 significance level using a parallel design the sample size needs to be 64 cases per group and 128 in all By accounting for 10 patients potentially withdrawing consent or being lost to follow-up over the course of the study the final sample size will be increased to 71 cases per arm and 142 patients in all
Planned Statistical Analysis
The primary analysis will be intention-to-treat The outcome of the superiority clinical trial will be assessed based on a two-sided 95 confidence interval around the mean VA and OCT outcome showing a credible range for true difference between merely corticosteroid and corticosteroid combined PE treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None