Pain, Postoperative Clinical Trial
Official title:
A Comparison of Analgesic and Respiratory Effects From Tapentadol Versus Oxycodone After Laparoscopic Hysterectomy.
Verified date | April 2019 |
Source | Oslo University Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Opioids remain the first-line drugs for the treatment of moderate to severe postoperative
pain, but the use is limited by well-known side-effects, most of which are dose-dependent.
The opioid oxycodone is standard therapeutic treatment for acute postoperative pain, either
in immediate-release formulation, OxyNorm®, or as extended-release formulation, OxyContin®.
Oxycodone provides analgesic effects through µ-opioid receptors in the central nervous
system.
Tapentadol hydrochloride/depot (Palexia/depot®) is a novel, centrally acting, strong
analgesic with a dual mechanism of action on µ-opioid receptors and noradrenaline reuptake in
the central nervous system. Tapentadol is an active compound, devoid of active metabolites
and not reliant on enzyme systems. For these reasons, it has a low drug interaction
potential. This dual mechanism also translates clinically into less adverse effects than with
pure opioid agonists like oxycodone. This is probably due to less µ-opioid receptor
stimulation.
Tapentadol has been shown effective in models of acute, osteoarthritic, neuropathic and
cancer pain. There is now an increasing use of tapentadol in postoperative pain treatment in
Norway. However, there is a lack of broad-based evidence for the use of tapentadol in the
post-surgical setting. So far, to our knowledge, there are only published studies on
postoperative pain treatment after orthopedic and dental surgery, but none related to deep
abdominal pain.
Tapentadol is shown in several studies on chronic pain patients to have comparable analgesic
effects to traditional opioid pain medications like oxycodone and morphine, but with a more
tolerable side-effect profile. In the postoperative setting after dental or orthopedic
surgery, studies have shown less nausea and constipation. It has also been suggested a lower
frequency of pruritus compared with oxycodone, but no difference in central nervous system
symptoms such as sleepiness or dizziness. The most dangerous side-effect from opioids is
respiratory depression with the potential of fatal outcome. The investigators have not found
any publications from short-term postoperative pain management comparing the respiratory
effect of tapentadol to the traditional opioids.
The aim of the study is to compare the analgesic effect and side-effects of this new
analgesic, tapentadol, to the standard treatment to day, oxycodone, in the acute
postoperative period after hysterectomy.
Status | Completed |
Enrollment | 86 |
Est. completion date | February 28, 2019 |
Est. primary completion date | February 28, 2019 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - Women diagnosed with a benign gynecological condition, undergoing laparoscopic, supra-cervical or total hysterectomy in general anesthesia. - Age 18-64 years. - ASA (American Society of Anesthesiologists) classification I-III. - Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonisation GCP, and national/local regulations. - The patients will be recruited from the patient population at the Department of Gynaecology. Exclusion Criteria: - Age under 18 or over 65. - BMI > 31 and/or weight <55 kg, >85 kg. - Chronic pain syndromes related to organ systems other than the female reproductive system. - Chronic opioid therapy (codeine medication allowed up to 60 mg/day) or enteral steroid therapy. - Alcohol or medical abuse/addiction. - Chronic obstructive pulmonary disease (spirometry with postbronchodilator FEV1/FVC ratio less than 0.7), untreated asthma (FEV1/FVC is reduced to less than 0.70), obstructive sleep apnea or other conditions known to predispose for respiratory depression. - Neurological diagnosis with affection of respiratory system or prone to seizures. - Previously diagnosed kidney (glomerular filtration rate <60 mL/min/1.73 m2 over 3 months) or liver impairment (ALAT > 45 U/L; ASAT > 35 U/L; ALP > 105 U/L; GT > 45 U/L age 18-39 or GT > 75 U/L age over 39; LD > 205 U/L). - Biliary tract disease. - Paralytic ileus. - Heart failure (NYHA III-IV). - Malignancy of any kind under treatment. Malignancy during last 5 years. - HIV infection. Infections of any kind affecting the patient's clinical status, i.e. upper or lower airway infection, urinary tract infection, deep wound infection. Infections not affecting the patient's clinical status, i.e. conjunctivitis, is not an exclusion criteria. - Untreated depression, severe anxiety or other psychiatric disorders independent of treatment. - Nursing mothers. - Cognitive failure, language barriers, hearing/visual disability or other factors which make follow-up difficult. - Allergy or contraindication to any of the medications used in the study. - Lactose intolerance. - Monoamine oxidase inhibitors or SNRI (serotonin norepinephrine reuptake inhibitors) within 14 days prior to randomization. SSRI (selective serotonin reuptake inhibitors) use is not an exclusion criterion if stable dose for at least 30 days before screening. - H1-antihistamine is not an exclusion criterion unless the patient experiences somnolence as a side-effect. - The concurrent use of benzodiazepines, barbiturates, neuroleptics, phenytoin tricyclic antidepressants, gabapentinoids, tramadol, clonidine, cimetidine, rifampicin, protease inhibitors, St John's wort (Hypericum perforatum), macrolides and antimycotics such as ketoconazole and fluconazole is not allowed. - Known complications to anesthesia or difficult airway (Definition of difficult airway: "The clinical situation in which a conventionally trained anesthesiologist experiences difficulty with mask ventilation, difficulty with tracheal intubation, or both."). - Patients who have participated in other clinical trials during the last 6 months are excluded to avoid confounders to the current study and for patient safety reasons. |
Country | Name | City | State |
---|---|---|---|
Norway | Oslo University Hospital | Oslo |
Lead Sponsor | Collaborator |
---|---|
Oslo University Hospital |
Norway,
Chang SH, Maney KM, Phillips JP, Langford RM, Mehta V. A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation. Anaesthesia. 2010 Oct;65(10):1007-12. doi: 10.1111/j.1365-2044.2010.06498.x. — View Citation
Daniels SE, Upmalis D, Okamoto A, Lange C, Häeussler J. A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (bunionectomy) pain. Curr Med Res Opin. 2009 Mar;25(3):765-76. doi: 10.1185/03007990902728183 . — View Citation
Hale M, Upmalis D, Okamoto A, Lange C, Rauschkolb C. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study. Curr Med Res Opin. 2009 May;25(5):1095-104. doi: 10.1185/03007990902816970 . — View Citation
Kleinert R, Lange C, Steup A, Black P, Goldberg J, Desjardins P. Single dose analgesic efficacy of tapentadol in postsurgical dental pain: the results of a randomized, double-blind, placebo-controlled study. Anesth Analg. 2008 Dec;107(6):2048-55. doi: 10.1213/ane.0b013e31818881ca. — View Citation
Langford RM, Knaggs R, Farquhar-Smith P, Dickenson AH. Is tapentadol different from classical opioids? A review of the evidence. Br J Pain. 2016 Nov;10(4):217-221. Epub 2016 Jul 25. — View Citation
Lee LA, Caplan RA, Stephens LS, Posner KL, Terman GW, Voepel-Lewis T, Domino KB. Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology. 2015 Mar;122(3):659-65. doi: 10.1097/ALN.0000000000000564. — View Citation
Raeder J. Opioids in the treatment of postoperative pain: old drugs with new options? Expert Opin Pharmacother. 2014 Mar;15(4):449-52. doi: 10.1517/14656566.2014.879292. Epub 2014 Jan 17. — View Citation
Ramaswamy S, Chang S, Mehta V. Tapentadol--the evidence so far. Anaesthesia. 2015 May;70(5):518-22. doi: 10.1111/anae.13080. — View Citation
Riley J, Eisenberg E, Müller-Schwefe G, Drewes AM, Arendt-Nielsen L. Oxycodone: a review of its use in the management of pain. Curr Med Res Opin. 2008 Jan;24(1):175-92. Review. — View Citation
Schröder W, Vry JD, Tzschentke TM, Jahnel U, Christoph T. Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. Eur J Pain. 2010 Sep;14(8):814-21. doi: 10.1016/j.ejpain.2010.05.005. Epub 2010 Jun 11. — View Citation
Stegmann JU, Weber H, Steup A, Okamoto A, Upmalis D, Daniels S. The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery . Curr Med Res Opin. 2008 Nov;24(11):3185-96. doi: 10.1185/03007990802448056 . Epub 2008 Oct 15. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Pain 1 hour postoperatively. | Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone. | 1 hour | |
Secondary | Pain 2 hours postoperatively. | Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone. | 2 hours | |
Secondary | Pain 3 hours postoperatively. | Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone. | 3 hours | |
Secondary | Pain 24 hours postoperatively. | Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone. | 24 hours | |
Secondary | Pain relief 30 minutes | Pain relief, measured with categorical scale "none, slight, moderate, good or complete", comparing pain at 30 minutes postoperatively to the previous measurement point. The measure "total pain relief" (TOTPAR) will be calculated from these values. | 30 minutes | |
Secondary | Pain relief 1 hour | Pain relief, measured with categorical scale "none, slight, moderate, good or complete", comparing pain at 1 hour postoperatively to the previous measurement point. The measure "total pain relief" (TOTPAR) will be calculated from these values. | 1 hours | |
Secondary | Pain relief 2 hours | Pain relief, measured with categorical scale "none, slight, moderate, good or complete", comparing pain at 2 hours postoperatively to the previous measurement point. The measure "total pain relief" (TOTPAR) will be calculated from these values. | 2 hours | |
Secondary | Pain relief 3 hours | Pain relief, measured with categorical scale "none, slight, moderate, good or complete", comparing pain at 3 hours postoperatively to the previous measurement point. The measure "total pain relief" (TOTPAR) will be calculated from these values. | 3 hours | |
Secondary | Pain relief 24 hours | Pain relief, measured with categorical scale "none, slight, moderate, good or complete", comparing pain at 24 hours postoperatively to the previous measurement point. The measure "total pain relief" (TOTPAR) will be calculated from these values. | 24 hours | |
Secondary | Global medication performance | The measure "Global medication performance" after 24 hours: the patient evaluates the overall satisfaction with the pain treatment on a scale ("poor, fair, good, very good, excellent"). | 24 hours | |
Secondary | Time to first rescue medicine | Time to first intravenous and/or per oral rescue medicine. | 24 hours | |
Secondary | Total rescue analgesic consumption | Total intravenous and per oral rescue analgesic consumption over 24 hours. | 24 hours | |
Secondary | Respiratory depression | Continuous measurement of end-tidal carbon dioxide (ETCO2) with Smart CapnoLine® Plus (Microstream®), data are collected at postoperatively. | 24 hours | |
Secondary | Respiratory rate | Respiratory rate at rest is measured postoperatively. | 24 hours |
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