Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain

December 9, 2015 updated by: Vinicius Borges Porfirio Pereira, University of Sao Paulo General Hospital

A Randomized Study of Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403-900
        • Universidade de São Paulo (USP) - Refractive surgery department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Codeine plus paracetamol
Codeine plus paracetamol every 6 hours for 72 hours after photorefractive keratectomy.
Drug: Codeine
Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure
Other Names:
  • 3-methylmorphine
Drug: paracetamol
Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure
Other Names:
  • acetaminophen
Placebo Comparator: placebo
Placebo every 6 hours for 72 hours after photorefractive keratectomy.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pain measured by visual-analog scale 24hour after PRK
Time Frame: 24hour
24hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Investigators

  • Study Director: Samir Bechara, MD, Universidade de São Paulo - USP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

November 29, 2015

First Submitted That Met QC Criteria

December 8, 2015

First Posted (Estimate)

December 9, 2015

Study Record Updates

Last Update Posted (Estimate)

December 11, 2015

Last Update Submitted That Met QC Criteria

December 9, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAAE : 37084214.3.0000.0068

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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