Phase 4 Study, Open, Observational, to Evaluate the Safety and Tolerability of Hydrochloride Controlled-release Oxycodone in Moderate and Severe Postoperative Pain in Oncologic Head and Neck Surgery.
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
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.
Time Perspective: Prospective
Number of participants with nausea
number of participants with nausea 48 hours after first dose of controlled-released oxycodone
48 hours post dose
Ismar L Cavalcanti, MD PhD
Instituto Nacional de Câncer Brazil
Brazil: Ministry of Health