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Botox Instead of Strabismus Surgery (BISS)

I

Insel Gruppe AG, University Hospital Bern

Status and phase

Completed
Phase 3

Conditions

Acquired Esotropia

Treatments

Drug: Botulinum toxin type A
Procedure: Strabismus surgery

Study type

Interventional

Funder types

Other

Identifiers

NCT03459092
33IC30 173533

Details and patient eligibility

About

The purpose of the study is to evaluate if strabismus can be successfully treated requiring less surgical interventions with a Botox-based treatment regimen compared to a purely surgery based treatment regimen.

Experimental arm: Botulinum toxin injection in the horizontal extraocular muscles.

Control (active comparator) arm: Strabismus surgery on the horizontal extraocular muscles. No investigational product is used.

In Switzerland the standard procedure for treating large angle esotropia is surgery, which is performed on the horizontal eye muscles that may be either recessed or shortened leading to reduced or increased muscle function respectively.

As an alternative to strabismus surgery, botulinum toxin (Botox) can be applied in extraocular muscles. Botox prevents the release of acetylcholine in the synaptic cleft and thereby blocks the neuromuscular transmission thus inducing a palsy.

Current evidence on the use of Botox in strabismus is incoherent, is poorly supported by basic research findings and leaves dedicated clinicians in the dark. The objective is to shed light into this field of clinical research, which may help to guide future pediatric ophthalmologists in their management of strabismic patients. In a best case scenario, the results from this trial will prevent strabismus operation for many children with acquired large angle esotropia.

Full description

Patients with acquired large angle esotropia (an inward deviation of the ocular axis by more than 5°) that develops after one year of age have a potential to regain binocular vision if a retinal image appears on corresponding retinal areas of both eyes. The main goal of therapy in these patients is the restoration of binocular vision.

In Switzerland the standard procedure for treating large angle esotropia is surgery, which is performed on the horizontal eye muscles that may be either recessed or shortened leading to reduced or increased muscle function respectively.

As an alternative to strabismus surgery, botulinum toxin (Botox) can be applied in extraocular muscles. Botox prevents the release of acetylcholine in the synaptic cleft and thereby blocks the neuromuscular transmission thus inducing a palsy.

Current evidence on the use of Botox in strabismus is incoherent, is poorly supported by basic research findings and leaves dedicated clinicians in the dark. The goal is to shed light into this field of clinical research, which may help to guide future pediatric ophthalmologists in their management of strabismic patients.

The goal of the study is to test if, with a botulinum-toxin-based treatment regimen, strabismus can be successfully treated requiring less surgical interventions.

The primary objective is to test if the Botox-based treatment regimen is not inferior to surgical treatment in terms of orthotropic success. If this is shown, the number of surgeries required will be compared between the two groups (main secondary objective).

The hypothesis is that the Botox-based treatment regimen, which permits performance of rescue surgery, is successful in a similar proportion of patients as the purely surgical approach. The second hypothesis is that only about 20% of patients treated with Botox require surgery at all as compared to about 10% of patients in the surgical arm that need a second surgery.

Analysis of the primary outcome The proportion of orthotropic success for both groups will be calculated with a corresponding 95% confidence interval. For the comparison between the two groups, the stratified risk difference for the stratification factors used in randomization will be calculated with a corresponding one-sided lower 95% confidence limit. If the lower limit lies above -12%, non-inferiority will be claimed.

Analysis of the main secondary outcome The proportion of second interventions for both groups will be calculated with a corresponding 95% confidence interval. For the comparison between the two groups, a stratified risk difference for the stratification factors used in randomization will be calculated with a corresponding one-sided upper 95% confidence limit. If the upper limit lies below 40% and if non-inferiority for the primary outcome could be demonstrated, a clinical benefit of the new treatment will be claimed.

Enrollment

63 patients

Sex

All

Ages

1 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Informed consent of trial participant and/or legal representative documented per signature

  2. Age > 1 year and <17 years

  3. Esotropia > 10Prisms

  4. Indication for an intervention (either Botox or surgery) has been made.

  5. Any of the following:

    • Presence of a secondary strabismus from binocular disruption the cause of the binocular disruption is no longer present
    • Decompensated microstrabismus
    • Decompensated phoria
    • Acute acquired esotropia
  6. Positive test of binocular function at any time point in the past, including any of the following

    • Titmus test
    • Bagolini striated glasses test
    • Lang-stereo-test with correct naming of at least one panel
    • Good ocular alignment after 6 months of age on at least 2 photographs

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 5°

  6. Incomitance with more than 5° 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. A negative pregnancy test before randomization is required for all women of child-bearing potential.

  11. Preterm children born before 36 weeks of gestation.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

63 participants in 2 patient groups

Botox-based treatment regimen
Experimental group
Description:
First intervention is a Botulinum toxin type A injection. If further treatment is necessary, strabismus surgery can be performed.
Treatment:
Drug: Botulinum toxin type A
Procedure: Strabismus surgery
Surgery-based treatment regimen
Active Comparator group
Description:
First intervention is strabismus surgery. If further treatment is necessary, strabismus surgery can be repeated.
Treatment:
Procedure: Strabismus surgery

Trial contacts and locations

8

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Data sourced from clinicaltrials.gov

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