Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain

NCT ID: NCT02625753

Last Updated: 2015-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2015-10-31

Brief Summary

Compare the use of codeine/paracetamol against placebo for pain control after cornea photorefractive keratectomy (PRK).

Detailed Description

The aim of this study was to measure pain during PRK postoperative period, comparing placebo with the association of codeine phosphate 30 mg and paracetamol 500 mg for 72h after surgery.

This is a double-blind, prospective, randomized study involving 80 eyes of 40 patients (paired design), who underwent photorefractive keratectomy at hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. The main outcome was the evaluation of pain by the Visual Analog Scale (VAS) 24h post-operatively.

Patients who had PRK as their chosen technique to correct their refractive errors were recruited for the study.

Patients had to be older than 20 years, with an spherical component between -1.00 and -5.00, with or without astigmatism, a cylindrical component up to 1.5D, spherical anisometropia of less than or equal to 0.75D, cylindrical anisometropia of less than or equal to 0.5D, stable refraction errors (maximal variation of 0.5D in the spherical or cylindrical component during 1 year) and amenable to follow-up for at least seven (7) days.

Exclusion criteria included the presence of active disease of allergic, inflammatory or infectious nature, in the ocular surface or its attachments; previous ocular history (pathology, surgery or ocular trauma); best corrected visual acuity less than 20/25); autoimmune disease, or immunosuppression or Diabetes Mellitus; pregnancy and lactation.

The same surgeon (VPBP) performed all procedures. Patients' eyes were operated at two-week intervals, and the treatment order (placebo or codein/paracetamol) was randomized for each patient.

The distribution of the continuous variables was assessed visually by constructing histograms. Due to moderately symmetrical feature of the data, parametric approaches were used, following the guidelines of Fagerland.18 Data were presented as mean ± standard deviation (SD) or mean (95% confidence interval), as appropriate. Counts and percentages were used to summarize binary variables.

The intervention effect was estimated by the difference between the average of the group treated eyes (μtreatment) and the mean of the control eyes group (μcontrol). In other words, the effect of treatment was estimated by the variable Δ where Δ = μtreatment - μcontrol. The statistical approach considered the paired nature of the study ("paired-eye design") following the recommendations of Armstrong et al. 19 Specifically, Δ was calculated taking into account the correlation between the pair of eyes. Covariates were included in the models of multiple linear regression, which were adjusted for age, gender (1 = male, 0 = female) and ancestry (0 = white 1 = brown and 2 = black). These models were built with a robust estimator of the variance, which incorporates the intra-patient correlation of the pair of eyes.20 Furthermore, due to the characteristic of repeated measurements (1h, 24h, 48h and 72h), for each variable, the p values were adjusted for multiple comparisons by the method of Holm- Šidák. 21,22 The relative magnitude of the variation of the treatment effect over time was examined by analysis of variance (ANOVA ) one-way repeated measures. This evaluation explicitly asks whether longitudinally, the effect of treatment, i.e., the magnitude of Δ is the same over time (H0 : Δ1h Δ24h = = = Δ48h Δ72h ). A Huynh-Feldt correction was applied. When statistically significant, ANOVA models were followed by post-hoc tests (paired student t test) to detect differences between specific times.

Potential predictors of the magnitude of the treatment effect were investigated having as the dependent variable Δ and the explanatory variables age, gender, ancestry, fractional error group (1 = -3 to -5, 0 = -1 to -3) and sequence of the treatment. No corrections were applied for multiple testing in the exploration of predictors of the magnitude of the treatment effect, since they were considered exploratory.

P values of the post-hoc tests were also adjusted for multiple comparisons using the Holm-Šidák method. The α significance level for all analyzes was 5%. The software used was Stata 13.0 (Stata Corporation, College Station, TX , USA).

Conditions

Myopia

Keywords

photorefractive keratectomy; pain; analgesia; opioid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Codeine plus paracetamol

Codeine plus paracetamol every 6 hours for 72 hours after photorefractive keratectomy.

Group Type: ACTIVE_COMPARATOR

Codeine

Intervention Type: DRUG

Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure

paracetamol

Intervention Type: DRUG

Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure

placebo

Placebo every 6 hours for 72 hours after photorefractive keratectomy.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Patients submmitted to photorefractive keratectomy received placebo, in the form of a pill of similar appearance to the comparator, every 6h for 72h after the

Interventions

Codeine

Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure

Intervention Type: DRUG

paracetamol

Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure

Intervention Type: DRUG

placebo

Patients submmitted to photorefractive keratectomy received placebo, in the form of a pill of similar appearance to the comparator, every 6h for 72h after the

Intervention Type: DRUG

Other Intervention Names

3-methylmorphine; acetaminophen

Eligibility Criteria

Inclusion Criteria

• older than 20 years
• spherical component between -1.00 and -5.00, with or without astigmatism
• cylindrical component up to 1.5D
• spherical anisometropia of less than or equal to 0.75D,
• cylindrical anisometropia of less than or equal to 0.5D,
• stable refraction errors (maximal variation of 0.5D in the spherical or cylindrical component during 1 year)
• amenable to follow-up for at least seven (7) days.

Exclusion Criteria

• presence of active disease of allergic, inflammatory or infectious nature, in the ocular surface or its attachments
• previous ocular history (pathology, surgery or ocular trauma)
• best corrected visual acuity less than 20/25)
• autoimmune disease, or immunosuppression or Diabetes Mellitus
• pregnancy or lactation.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Vinicius Borges Porfirio Pereira

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Samir Bechara, MD

Role: STUDY_DIRECTOR

Universidade de São Paulo - USP

Locations

Universidade de São Paulo (USP) - Refractive surgery department

São Paulo, São Paulo, Brazil

Countries

Brazil

References

Pereira VBP, Torriceli AAM, Garcia R, Bechara SJ, Alves MR. Codeine plus acetaminophen improve sleep quality, daily activity level, and food intake in the early postoperative period after photorefractive keratectomy: a secondary analysis. Arq Bras Oftalmol. 2021 Jan-Feb;84(1):45-50. doi: 10.5935/0004-2749.20210008.

Reference Type: DERIVED

PMID: 33470341 (View on PubMed)

Pereira VBP, Garcia R, Torricelli AAM, Mukai A, Bechara SJ. Codeine Plus Acetaminophen for Pain After Photorefractive Keratectomy: A Randomized, Double-Blind, Placebo-Controlled Add-On Trial. Cornea. 2017 Oct;36(10):1206-1212. doi: 10.1097/ICO.0000000000001328.

Reference Type: DERIVED

PMID: 28820793 (View on PubMed)

Other Identifiers

CAAE : 37084214.3.0000.0068

Identifier Type: -

Identifier Source: org_study_id