Safety and Tolerability of Controlled-release Oxycodone on Postoperative Pain in Oncologic Head and Neck Surgery
Condition: Postoperative Nausea; Adverse Effects; Opioid Analgesic Adverse Reaction; Pain
MeSH terms: Pain, Postoperative; Postoperative Nausea and Vomiting
Study type: Observational

Summary: 
      The hypothesis of this study is that controlled release oxycodone can be safe and well
      tolerated for the control of postoperative pain in surgery for head and neck cancer. The
      primary objective is to study the safety and the incidence and severity of adverse effects,
      and the secondary objective is to evaluate the analgesic efficacy and identify the frequency
      of use of rescue medication and the prescribing physician's opinion about the quality of
      postoperative analgesia with oxycodone controlled release in oncologic surgery of the head
      and neck.
    

Detailed description: 
      Phase IV clinical trial, observational, prospective, open approved by the Research Ethics
      Committee of the National Cancer Institute José Alencar Gomes da Silva - INCA, Brazil (no.
      10/2010). The Instrument of Consent is signed by all patients.

      Eighty-three patients will be included. Ages between 18 and 70 years both genders, 2 and 3
      American Society of Anesthesiologists physical status, which present moderate to severe pain
      source postoperative surgical oncology, head and neck, medium and large, elective,
      non-emergency, able to swallow tablets whole (not chewed, broken or crushed) in the immediate
      postoperative period after recovery of cognitive functions. Will be excluded pregnant or
      breastfeeding, allergic to oxycodone and other opioids, gastrectomized or colostomized,
      asthmatics with severe organ dysfunction, with a history or suspected paralytic ileus, or a
      history psychiatric disorders, severe respiratory depression, patients who are receiving
      opioid analgesics in baseline, history of abuse of alcohol and illicit drugs, patients who
      present in plasma glutamic oxaloacetic transaminase above 48 U / l (men) and 40 U / I (women)
      and / or glutamic pyruvic transaminase above 53 U / l (men) and 40 U / I (women) and patients
      who present plasma creatinine above 1.7 mg / dl and / or urea above 65 mg / dl. All patients
      will be assessed preoperatively seven to one day before surgery (visit 1) when will the
      signed consent form, proceeded to pre-anesthetic evaluation and blood will be collected for
      laboratory tests: complete blood count, β-human chorionic gonadotropin(women), glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase, creatinine and urea.

      In the immediate postoperative period (visit 2), the pain will be assessed by verbal numeric
      scale (VNS) and when pain is moderate to severe (≥ 4 EVN) and the patient is lucid and able
      to swallow, will start orally controlled-release oxycodone (Oxycontin, Zodiac
      Pharmaceuticals, Brazil) at a dose of 20 mg (tablets whole without crushing or division),
      administered by the investigator. Every 12 hours and a subsequent period of 48 hours after
      the first dose of oxycodone controlled-release, the pain will be evaluated again, and the
      occurrence and intensity of adverse events (visits 3, 4, 5 and 6 respectively 12 , 24, 36 and
      48 hours after the first dose of oxycodone). The doses of controlled-release oxycodone will
      be standardized as follows: on the first day postoperatively, 40 mg / day divided into 20 mg
      of 12 in 12 hours and in the second postoperative day, 20 mg / day divided into 10 mg of 12
      in 12 hours.

      The rescue medication will be used non opioids analgesics as paracetamol, dipyrone,
      diclofenac or tenoxicam, only after the first administration of controlled-release oxycodone
      postoperatively. During the visits described above will be annotated to rescue analgesia and
      its frequency, should it ever be used between doses of oxycodone.

      Between post-operative 7 and 13 days will be held the visit 7, which will be evaluated pain
      intensity (EVN), the occurrence and severity of adverse effects, and the investigator's
      opinion about treatment. Finally, the patient's blood will be collected to perform the same
      tests listed at visit 1, except β-human chorionic gonadotropin (women), and the study was
      terminated.

      Sample Size and Statistical Analysis

      When considering the occurrence of nausea of 25% as a safety parameter, assessed by
      literature data, the number of patients required will be 72. Taking into consideration a
      dropout of about 20% will require 86 patients in total (to an accuracy of 10%, around the
      percentage confidence interval (CI) 95%). The study of normal age variable will be conducted
      with the test Kolmogorov - Smirnov. The Friedman test is used to compare medians of pain
      intensity from visit 2 to visit 7. The Dunn test will be used for post-hoc comparisons
      (between two) of median pain intensity (p <0.001 - significant). The McNemar test for
      pairwise comparisons of proportions will be employed for comparisons of adverse events
      (visits 4, 5, 6 and 7 with respect to visit 3) (p <0.05 = significant). The remaining data
      will be presented by frequency.
    

Intervention name(s): Controlled-release oxycodone
Intervention type(s): Drug
Intervention description(s): Controlled-release oxycodone. First day postoperatively, 40 mg / day divided into 20 mg of 12 in 12 hours and in the second postoperative day, 20 mg / day divided into 10 mg of 12 in 12 hours
Other intervention name(s): Opioid; Postoperative analgesia; Postoperative pain
Intervention MeSH terms: Oxycodone
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients on postoperative head and neck oncologic surgery which moderate to severe pain
      
Keywords: postoperative; analgesia; adverse effects; opioid; oxycodone