Effects of Tapentadol Versus Oxycodone After Hysterectomy.
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|ClinicalTrials.gov Identifier: NCT03314792|
Recruitment Status : Completed
First Posted : October 19, 2017
Last Update Posted : April 4, 2019
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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.
|Condition or disease||Intervention/treatment||Phase|
|Pain, Postoperative Pain Uterus Pain, Acute Opioid Use Analgesics, Antipyretics, and Antirheumatics Causing Adverse Effects in Therapeutic Use Visceral Pain||Drug: Tapentadol Drug: Oxycodone||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||86 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Masking Description:||Patients were not told which medicine they were given, but due to difference in apperance of pills they would be able to find out which medicine they were given if they wanted to. Care providers at the hospital ward administering the medication would know which medicine were given due to apperance.|
|Official Title:||A Comparison of Analgesic and Respiratory Effects From Tapentadol Versus Oxycodone After Laparoscopic Hysterectomy.|
|Actual Study Start Date :||December 4, 2017|
|Actual Primary Completion Date :||February 28, 2019|
|Actual Study Completion Date :||February 28, 2019|
Active Comparator: Oxycodone
Active comparator drug administrated.
Experimental drug administrated.
- Pain 1 hour postoperatively. [ Time Frame: 1 hour ]Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone.
- Pain 2 hours postoperatively. [ Time Frame: 2 hours ]Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone.
- Pain 3 hours postoperatively. [ Time Frame: 3 hours ]Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone.
- Pain 24 hours postoperatively. [ Time Frame: 24 hours ]Difference in scoring of pain at rest using the numerical rating scale for pain between the two intervention groups, tapentadol and oxycodone.
- Pain relief 30 minutes [ Time Frame: 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.
- Pain relief 1 hour [ Time Frame: 1 hours ]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.
- Pain relief 2 hours [ Time Frame: 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.
- Pain relief 3 hours [ Time Frame: 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.
- Pain relief 24 hours [ Time Frame: 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.
- Global medication performance [ Time Frame: 24 hours ]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").
- Time to first rescue medicine [ Time Frame: 24 hours ]Time to first intravenous and/or per oral rescue medicine.
- Total rescue analgesic consumption [ Time Frame: 24 hours ]Total intravenous and per oral rescue analgesic consumption over 24 hours.
- Respiratory depression [ Time Frame: 24 hours ]Continuous measurement of end-tidal carbon dioxide (ETCO2) with Smart CapnoLine® Plus (Microstream®), data are collected at postoperatively.
- Respiratory rate [ Time Frame: 24 hours ]Respiratory rate at rest is measured postoperatively.
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|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
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): NCT03314792
|Oslo University Hospital|
|Oslo, Norway, 0424|
|Principal Investigator:||Harald Lenz, MD, PhD||Oslo University Hospital|
Documents provided by Harald Lenz, Oslo University Hospital:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Harald Lenz, Principal investigator, Oslo University Hospital|
|Other Study ID Numbers:||
|First Posted:||October 19, 2017 Key Record Dates|
|Last Update Posted:||April 4, 2019|
|Last Verified:||April 2019|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||The study has no collaborators outside Oslo University Hospital and individual participant data (IPD) is not planned shared with other researchers during the study periode. The database with IPD will be stored in a secure research server at Oslo University Hospital according to the policy for secure storage.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
|Time Frame:||The database will be stored until 31.12.2035.|
Sponsor's representatives (e.g. monitors, auditors) and/or competent authorities will be allowed access to source data for source data verification.
The sponsor has the right to share IPD underlying the results presented in the final published article should any journal or editor require this. The data underlying the results are defined as the IPD required to reproduce the article's findings, including necessary metadata.
Other research groups may be granted access to the data upon request after publishing of the article. This will be according to the relevant journal's requirements for data sharing upon publishing. The research must have relevant connection to the original study and the research group must fulfill requirements for safe storage and handling of data. The patients are informed of potential data sharing in the informed consent form. The confidentiality guidelines of Oslo University Hospital and the regional ethics committee will at all times be followed.
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
postoperative pain management
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action