Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm

The University of Hong Kong (HKU)

Status and phase: Completed; Phase 4

Conditions: Botulinum Toxins, Type A; Blepharospasm; Hemifacial Spasm

Treatments: Drug: Saline Solution for Injection; Drug: Botulinum Toxin Type A 100Unit/Vial (Product)

Study type: Interventional

Funder types: Other

Identifiers

NCT03508882

HMRF Project No.: 12133171

Protocol : MMBT ( v1.3;1Mar16;Other Identifier)

Details and patient eligibility

About

A triple-masked placebo-controlled trial assessing the efficacy and safety of pretarsal versus preseptal botulinum toxin for patients with eyelid spasm. The investigators hypothesize injection of botulinum toxin into the pretarsal orbicularis oculi muscle will have greater clinical efficacy, better measured quality of life, fewer complications, and better cost effectiveness in comparison to a preseptal pattern of injection.

Full description

The study design is a prospective, randomized, triple-blinded placebo controlled crossover trial. A computer-generated list of random numbers will be used for allocation of patients. The patients, treating physicians, and outcome assessors will be masked to the contents of the Botulinum Toxin Type A (BtA) and placebo syringe injections. The placebo will consist of vehicle only, which is the same sterile normal 0.9% saline used in reconstitution of the BtA. At month 6, each group will crossover and receive the alternative intervention. The primary outcome measure (JRS severity) will be the change as measured 1 month after the second cycle of each intervention. Secondary outcome measures include the TWSTRS (clinical response), Blepharospasm Disability Index (BSDI), CDQ-24 (quality of life), VAS (pain), and GAS (global) scores and incidence of side effects. The investigators plan to compare the outcome measures between groups with linear mixed models allowing for the crossover design.

Data will be collected at each of the injection visits and at both of the clinical activity visits. The data will be processed by the research assistant and analysed by the project biostatistician. The investigators plan to compare the primary (JRS) and secondary outcome measures (TWSTRS, BSDI, CDQ-24, VAS, and GAS scores) between the Preseptal-pretarsal (Group 1) and the Pretarsal-preseptal (Group 2) allowing for the crossover design. Specifically, the investigators will use a 2-sample t-test to compare all values of the JRS in group 1 with all the values of the JRS in group 2. This will allow the investigators to determine whether carryover effects are present, and the investigators have specified a 3-month washout period between the first and second round of injections to minimise the chance of carryover effects. If carryover effects are present, the investigators will allow for these in further analysis. The investigators will then use linear mixed models to estimate the difference between the two interventions, allowing for the repeated measures, and if necessary for carryover effects. In secondary analyses, the investigators will evaluate the proportion of patients with relief of spasm, improvement in quality of life, and incidence of side effects, including eyelid ptosis measurements between the two interventions, using logistic regression. P values of 0.05 or less will be considered statistically significant. All analyses will be conducted under the principle of Intention to Treat, using multiple imputation to account for any missing data and to include all randomized patients in analysis.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients over 18 years-of-age
• Clinical diagnosis eyelid dystonia, consisting of either blepharospasm or hemifacial spasm
• Patient wish to have treatment with botulinum toxin type A (BtA).

Exclusion criteria

• Patients unable to express their symptoms or history to the extent that they are not able to complete the study questionnaires, such as those suffering from dementia.

• Existence of potential contraindications to BtA treatment:

  • Pregnancy
  • Breastfeeding
  • Prior allergic reaction
  • Active infection or inflammation in the treatment area
  • Neuromuscular and peripheral neuropathic disease
  • Concomitant aminoglycoside therapy

• Patients with poor or unstable general health with activities of daily living severely affected by non-dystonia confounding factors, such as hospitalized or bed bound patients.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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100 participants in 2 patient groups

Preseptal-pretarsal

Active Comparator group

Description:

The Preseptal-pretarsal group will receive injections of Botulinum Toxin Type A 100Unit/Vial (Product) in the preseptal site (Injection pattern A) and Saline Solution for Injection (placebo control) in the pretarsal site for 2 cycles at 3 months apart. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

Treatment:

Drug: Saline Solution for Injection

Drug: Botulinum Toxin Type A 100Unit/Vial (Product)

Pretarsal-preseptal

Active Comparator group

Description:

The Pretarsal-preseptal group will initially receive injections Botulinum Toxin Type A 100Unit/Vial (Product) in the reverse with the intervention at the pretarsal site (Injection pattern B) for 2 cycles at 3 months apart. Groups 1 and 2 will crossover and receive the alternative intervention. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

Treatment:

Drug: Saline Solution for Injection

Drug: Botulinum Toxin Type A 100Unit/Vial (Product)