Traumatic Optic Neuropathy Treatment Trial 2

NCT03308448 | Completed Phase 3

• 1 other identifier: IUMS 96-03-124-31806
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Traumatic Optic Neuropathy

Keywords

Traumatic optic neuropathy; Erythropoietin; EPO; Eprex

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

  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

  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)

  before treatment and on day 1, 2 and 3 after treatment.

Study Arms (3)

Group 1

ACTIVE COMPARATOR

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

Group 2

ACTIVE COMPARATOR

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

Group 3

ACTIVE COMPARATOR

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

Interventions

Recombinant human erythropoietin DRUG

Intravenous administration of recombinant human erythropoietin (4000 u/vial) with different dosage for each group

Also known as: EPO, Eprex

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Iran University of Medical Sciences: lead
• Mashhad University of Medical Sciences: collaborator
• Tehran University of Medical Sciences: collaborator

Study Sites (3)

Iran University of Medical Sciences

Tehrān, Tehran Province, Iran

Location

Mashhad University of Medical Sciences

Mashhad, Iran

Location

Tehran University of Medical Sciences

Tehran, Iran

Location

Related Publications (4)

• Kashkouli MB, Pakdel F, Sanjari MS, Haghighi A, Nojomi M, Homaee MH, Heirati A. Erythropoietin: a novel treatment for traumatic optic neuropathy-a pilot study. Graefes Arch Clin Exp Ophthalmol. 2011 May;249(5):731-6. doi: 10.1007/s00417-010-1534-3. Epub 2010 Oct 2.

  PMID: 20890611 BACKGROUND

• Entezari M, Esmaeili M, Yaseri M. A pilot study of the effect of intravenous erythropoetin on improvement of visual function in patients with recent indirect traumatic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2014 Aug;252(8):1309-13. doi: 10.1007/s00417-014-2691-6. Epub 2014 Jul 2.

  PMID: 24986593 BACKGROUND

• Kashkouli MB, Yousefi S, Nojomi M, Sanjari MS, Pakdel F, Entezari M, Etezad-Razavi M, Razeghinejad MR, Esmaeli M, Shafiee M, Bagheri M. Traumatic optic neuropathy treatment trial (TONTT): open label, phase 3, multicenter, semi-experimental trial. Graefes Arch Clin Exp Ophthalmol. 2018 Jan;256(1):209-218. doi: 10.1007/s00417-017-3816-5. Epub 2017 Oct 6.

  PMID: 28986670 BACKGROUND

• Abdolalizadeh P, Kashkouli MB, Ghazizadeh M, Pakdel F, Etezad Razavi M, Nojomi M, Abri Aghdam K, Sanjari MS, Karimi N, Ghahvehchian H, Soleimani M, Tabatabaei SA. Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin - a multicentre, randomised, double-blind clinical trial. Br J Ophthalmol. 2025 Mar 20;109(4):525-532. doi: 10.1136/bjo-2024-325828.

  PMID: 39461733 DERIVED

MeSH Terms

Conditions

Optic Nerve Injuries

Interventions

Epoetin Alfa

Condition Hierarchy (Ancestors)

Cranial Nerve Injuries; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases; Craniocerebral Trauma; Trauma, Nervous System; Eye Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Mohsen B Kashkouli, MD

  Iran University of Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants are unaware of the dose of EPO. Outcome assessors are masked to the dose of EPO
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 treatment groups of patients with TON will receive different total dose of EPO.

Study Record Dates

• First Submitted: September 24, 2017
• First Posted: October 12, 2017
• Study Start: January 6, 2018
• Primary Completion: August 6, 2022
• Study Completion: March 2, 2023
• Last Updated: March 8, 2024

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: It will be published in around February 2024 and will be available for 6 months
• Access Criteria: It will be available for all the researchers

Locations

IR (3)