Traumatic Optic Neuropathy Treatment Trial 2

Study Overview
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Brief Summary
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After introducing intravenous erythropoietin (EPO) as an option for treatment of patients with indirect traumatic optic neuropathy in 2011 and publishing non inferiority trial in Oct.2017), TONTT2 is aiming to find out the best dose and timing of EPO administration in this group of patients.

Detailed Description
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Patients with TON will be visited. After being eligible to enter the study and obtaining informed consent, they will be randomly assigned into 3 groups of different total dose of intravenous administration of EPO to which patients and outcome assessors will be masked. They will be assessed at different follow up time periods with the last follow up of at least 3 months.

Official Title
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Traumatic Optic Neuropathy Treatment Trial 2; Efficacy of Different Doses of Erythropoietin. A Multicenter, Double Blind RCT

Conditions
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Traumatic Optic Neuropathy

Intervention / Treatment
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* Drug: Recombinant human erythropoietin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having indirect traumatic optic neuropathy(with normal eye and fundus exam) Trauma to treatment interval of 3 weeks and less Age of 7 years and more Exclusion Criteria: Direct optic neuropathy, Glaucoma, Any retinopathy Globe laceration Age under 7 Hypertension, Polycythemia, Creatinin more than 3 mg/dl, Sensitivity to EPO Patients who have received any other form of treatment for their traumatic optic neuropathy

Ages Eligible for Study
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Minimum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 treatment groups of patients with TON will receive different total dose of EPO.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Intervention is Intra-Venous injection of Eprex or EPO [recombinant human erythropoietin, Pooyesh Darou Biopharmaceuticals CO., Tehran, Iran, 4000 unit/ml solution in prefilled syringe], 300 units/kg/day for three consecutive days (total:900/kg in 3 days) | Drug: Recombinant human erythropoietin<br>* Intravenous administration of recombinant human erythropoietin (4000 u/vial) with different dosage for each group<br>* Other names: EPO, Eprex;|
| Active Comparator: Group 2<br>Intervention is Intra-Venous injection of Eprex or EPO [recombinant human erythropoietin, Pooyesh Darou Biopharmaceuticals CO., Tehran, Iran, 4000 unit/ml solution in prefilled syringe], 600 units/kg/day for three consecutive days (total:1800/kg in 3 days) | Drug: Recombinant human erythropoietin<br>* Intravenous administration of recombinant human erythropoietin (4000 u/vial) with different dosage for each group<br>* Other names: EPO, Eprex;|
| Active Comparator: Group 3<br>Intervention is Intra-Venous injection of Eprex or EPO [recombinant human erythropoietin, Pooyesh Darou Biopharmaceuticals CO., Tehran, Iran, 4000 unit/ml solution in prefilled syringe], 600 units/kg/day for three consecutive days then repetition of the same treatment in month 1 (Total: 3600/kg in 2 set of 3-day treatment, 1 month apart) | Drug: Recombinant human erythropoietin<br>* Intravenous administration of recombinant human erythropoietin (4000 u/vial) with different dosage for each group<br>* Other names: EPO, Eprex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean LogMAR Best corrected visual acuity (BCVA) from 20/20 to no light perception (NLP) as assessed by Snellen visual acuity chart and analyzed based on mean LogMAR change. | Best corrected Visual acuity is measured (Snellen eye chart) and recorded as 20/20-20/25, 20/30, 20/40, 20, 50, 20/70, 20/100, 20/200 and then counting finger (CF), hand motion (HM), light perception (LP), and no light perception (NLP) | Before treatment and on day 1,2,3, 7, 30, and 90 days after the treatment and through study completion, an average of 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Log Unit of Relative afferent pupillary defect (RAPD) from 0.3 to 1.8 log unit as assessed by Neutral density filter | RAPD will be measured based on six log unit of 0.3, 0.6, 0.9, 1.2, 1.5,and 1.8 in which the higher the number the higher the severity score of RAPD. | Before treatment and on day 1,2,3, 7, 30, and 90 days after the treatment and through study completion, an average of 24 months | 
| Change in Mean number of visible color plates in Color vision test book. It is from 14/14 to 0/14 as assessed by Ishihara 14-plate color test book | Using Ishihara 14-plate color vision test book, the color vision will be recorded as a fraction of 14 plates; e.g. 10/14. Patients with lower than 20/200 vision will have 0/14 since they can not read the color plates. | Before treatment and on day 1,2,3, 7, 30, and 90 days after the treatment and through study completion, an average of 24 months | 
| Number of patients with treatment related adverse effects as assessed by history taking (change in mood, vertigo, faint), examination (blood pressure) and blood tests (CBC, BUN, Cr., K, Na, PT, PTT, INR, Ca., Ph) | history taking (change in mood, vertigo, faint), examination (blood pressure) and blood tests (CBC, BUN, Cr., K, Na, PT, PTT, INR, Ca., Ph) will be performed before treatment and on day 1, 2 and 3 after treatment. | before treatment and on day 1, 2 and 3 after treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic optic neuropathy, Erythropoietin, EPO, Eprex