Botox Instead of Strabismus Surgery (BISS)

A pragmatic, randomized, non-inferiority trial comparing the effectiveness of Botulinum toxin-based treatment with conventional strabismus surgery in acquired esotropia - BISS study

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-000280-23-FR

Enrollment

140

Registered

2020-07-10

Start date

2020-08-20

Completion date

Unknown

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acquired esotropia (strabismus) MedDRA version: 20.0 Level: LLT Classification code 10015475 Term: Esotropia System Organ Class: 100000004853 MedDRA version: 20.0 Level: LLT Classification code 10042163 Term: Strabismus NOS System Organ Class: 100000004853

Interventions

Trade Name: Botox Product Name: Botox Pharmaceutical Form: Powder for solution for injection

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Informed consent of trial participant and/or legal representative documented per signature 2.Age > 1 and =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1.Known hypersensitivity to botulinum toxin 2.Known neuromuscular disorder 3.Known present neurological disorder affecting the central nervous system Including paresis on cranial nerves number 3, 4 and 6 4.Any of the following: •nystagmus •dissociated vertical deviation 5.Vertical deviation in any gaze direction greater than 10? 6.Incomitance with more than 10? of difference between the left and right horizontal gaze direction 7.Previous strabismus surgery 8.Previous botulinum toxin treatment on extraocular muscles 9.Presence of ophthalmic pathologies significantly preventing binocular functions. A significant alteration of binocular function is assumed if vision is smaller than 0.1 or the visual field has a horizontal diameter of less than 20°. 10.Pregnancy or breastfeeding. A negative pregnancy test before randomization is required for female participants with childbearing potential (i.e. subjects who have reached menarche). 11.Preterm children born before 36 weeks of gestation.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of the study is to assess the effectiveness of a Botox-based treatment regimen compared to a purely surgery-based treatment regimen in terms of binocular vision at 18 months.;Secondary Objective: The main secondary objective is to assess secondary interventions in the Botox-based treatment arm compared to the purely surgery-based treatment arm at 18 months. Other secondary objectives are to evaluate the presence of binocular vision in each treatment arm at 12 months, the number of secondary interventions within 12 months, the number of surgeries per participant and per case with binocular vision up to 12 and 18 months and the effect of treatment on the strabismus angle at 12 and 18 months, the total ocular deviation (phoria and tropia) at the different time points and the horizontal incomitance. Incomitance is a gaze dependent variation of a strabismus angle, which usually results from changes in ocular motility. ;Primary end point(s): The primary outcome is presence of binocular vision at 18 months. The rational for the primary outcome is that the main goal of therapy in patients with acquired large angle esotropia is the restoration of binocular vision. Presence of binocular vision is a binary variable set to yes when either of the following criteria is fulfilled: 1.No eye movement can be observed in the simultaneous prism covertest, performed according to the study specific SOP for full orthoptic workup, for both eyes measured at distance. This proves orthotropia and thus binocular vision can be assumed. 2.An esotropia of less than 10? is observed in the covertest at distance AND at near. In addition at least one of the binocular tests demonstrates binocular vision. This proves compensated microstrabismus with anomalous retinal correspondence. ;Timepoint(s) of evaluation of this end point: 18 months	—

Measure

Time frame

Main Objective: The primary objective of the study is to assess the effectiveness of a Botox-based treatment regimen compared to a purely surgery-based treatment regimen in terms of binocular vision at 18 months.;Secondary Objective: The main secondary objective is to assess secondary interventions in the Botox-based treatment arm compared to the purely surgery-based treatment arm at 18 months. Other secondary objectives are to evaluate the presence of binocular vision in each treatment arm at 12 months, the number of secondary interventions within 12 months, the number of surgeries per participant and per case with binocular vision up to 12 and 18 months and the effect of treatment on the strabismus angle at 12 and 18 months, the total ocular deviation (phoria and tropia) at the different time points and the horizontal incomitance. Incomitance is a gaze dependent variation of a strabismus angle, which usually results from changes in ocular motility. ;Primary end point(s): The primary outcome is presence of binocular vision at 18 months. The rational for the primary outcome is that the main goal of therapy in patients with acquired large angle esotropia is the restoration of binocular vision. Presence of binocular vision is a binary variable set to yes when either of the following criteria is fulfilled: 1.No eye movement can be observed in the simultaneous prism covertest, performed according to the study specific SOP for full orthoptic workup, for both eyes measured at distance. This proves orthotropia and thus binocular vision can be assumed. 2.An esotropia of less than 10? is observed in the covertest at distance AND at near. In addition at least one of the binocular tests demonstrates binocular vision. This proves compensated microstrabismus with anomalous retinal correspondence. ;Timepoint(s) of evaluation of this end point: 18 months

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Secondary

Measure	Time frame
Secondary end point(s): The main secondary outcome is •Second intervention (yes/no) within 18 months (i.e. rescue surgery in Botox-based treatment arm and second surgery in surgery arm) This outcome is directly linked to the success rate of the two compared interventions, botulinum toxin injection and strabismus surgery. Further secondary outcomes are •Binocular vision, at 12 months •Second intervention as defined above, within 12 months •Incomitance at 12 and 18 months Incomitance is here defined as the absolute difference of strabismus angle measured with the alternate prism cover test at 25° left gaze and the angle measured at 25° right gaze. •Treatment-specific presence of binocular vision (yes/no) at 12 and 18 months For this outcome patients with a second intervention are defined as failures (no). •Number of surgeries per participant at 12 and 18 months •Number of surgeries needed per successful outcome (binocular vision) at 12 and 18 months •Change in strabismus angle, measured as percentage of preoperative deviation, from baseline to 12 and 18 months. The strabismus angle measured with the alternate prism cover test, performed according to the study specific SOP for full orthoptic workup, in primary position at distance is used. Change of deviation in percent of preoperative deviation is calculated as follows: 100*(preoperative deviation – postoperative deviation) / preoperative deviation •Binocular function at 12 and 18 months ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation for secondary endpoints are specified within each definition of secondary endpoints (see E.5.2)	—

Measure

Time frame

Secondary end point(s): The main secondary outcome is •Second intervention (yes/no) within 18 months (i.e. rescue surgery in Botox-based treatment arm and second surgery in surgery arm) This outcome is directly linked to the success rate of the two compared interventions, botulinum toxin injection and strabismus surgery. Further secondary outcomes are •Binocular vision, at 12 months •Second intervention as defined above, within 12 months •Incomitance at 12 and 18 months Incomitance is here defined as the absolute difference of strabismus angle measured with the alternate prism cover test at 25° left gaze and the angle measured at 25° right gaze. •Treatment-specific presence of binocular vision (yes/no) at 12 and 18 months For this outcome patients with a second intervention are defined as failures (no). •Number of surgeries per participant at 12 and 18 months •Number of surgeries needed per successful outcome (binocular vision) at 12 and 18 months •Change in strabismus angle, measured as percentage of preoperative deviation, from baseline to 12 and 18 months. The strabismus angle measured with the alternate prism cover test, performed according to the study specific SOP for full orthoptic workup, in primary position at distance is used. Change of deviation in percent of preoperative deviation is calculated as follows: 100*(preoperative deviation – postoperative deviation) / preoperative deviation •Binocular function at 12 and 18 months ;Timepoint(s) of evaluation of this end point: Timepoints of evaluation for secondary endpoints are specified within each definition of secondary endpoints (see E.5.2)

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Countries

France, Switzerland

Contacts

Public ContactMathias Abegg

Mathias Abegg

mathias.abegg@insel.ch41316322111

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026