Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain

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ClinicalTrials.gov Identifier: NCT02625753

Recruitment Status : Completed

First Posted : December 9, 2015

Last Update Posted : December 11, 2015

Sponsor:

Information provided by (Responsible Party):

Vinicius Borges Porfirio Pereira, University of Sao Paulo General Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Myopia	Drug: Codeine Drug: paracetamol Drug: placebo	Phase 3

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized Study of Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain
Study Start Date :	November 2014
Actual Primary Completion Date :	June 2015
Actual Study Completion Date :	October 2015

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Nearsightedness

Drug Information available for: Codeine

U.S. FDA Resources

Arms and Interventions

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 Name: 3-methylmorphine Drug: paracetamol Patients submitted to photorefractive keratectomy received codeine 50mg plus paracetamol 500mg every 6h for 72h after the procedure Other Name: 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

Outcome Measures

Primary Outcome Measures :

Pain measured by visual-analog scale 24hour after PRK [ Time Frame: 24hour ]

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02625753

Locations

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

Sponsors and Collaborators

University of Sao Paulo General Hospital

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Vinicius Borges Porfirio Pereira, MD, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:	NCT02625753
Other Study ID Numbers:	CAAE : 37084214.3.0000.0068
First Posted:	December 9, 2015 Key Record Dates
Last Update Posted:	December 11, 2015
Last Verified:	December 2015

Keywords provided by Vinicius Borges Porfirio Pereira, University of Sao Paulo General Hospital:


photorefractive keratectomy pain analgesia opioid

Additional relevant MeSH terms:

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Pain, Postoperative Postoperative Complications Pathologic Processes Pain Neurologic Manifestations Signs and Symptoms Acetaminophen Codeine Analgesics, Non-Narcotic Analgesics	Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Antipyretics Analgesics, Opioid Narcotics Central Nervous System Depressants Antitussive Agents Respiratory System Agents

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