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Effects of Tapentadol Versus Oxycodone After Hysterectomy.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03314792
Recruitment Status : Completed
First Posted : October 19, 2017
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Harald Lenz, Oslo University Hospital

Brief Summary:

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

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
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.
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hysterectomy

Arm Intervention/treatment
Active Comparator: Oxycodone
Active comparator drug administrated.
Drug: Oxycodone
  • OxyContin 10 mg® (oxycodone extended-release 10 mg): Administered by the patient as oral premedication 1 hour before scheduled start of surgery. OxyContin is repeated once after 12 hours.
  • OxyNorm 10 mg® (oxycodone immediate-release 10 mg): Administered as oral rescue medicine. First possible administration in postoperative ward when the patient is awake and available for oral medication. Maximum 4 capsules/24-hour study period. Minimum 1 hour 15 minutes between capsules. The patient is instructed to take 1 tablet if pain is increasing and the minimum period since last tablet is exceeded.

Experimental: Tapentadol
Experimental drug administrated.
Drug: Tapentadol
  • Palexia depot 50 mg® (tapentadol depot 50 mg): Administered by the patient as oral premedication 1 hour before scheduled start of surgery. Palexia depot is repeated once after 12 hours.
  • Palexia 50 mg® (tapentadol 50 mg): Administered as oral rescue medicine. First possible administration in postoperative ward when the patient is awake and available for oral medication. Maximum 4 tablets/24-hour study period. Minimum 1 hour 15 minutes between tablets. The patient is instructed to take 1 tablet if pain is increasing and the minimum period since last tablet is exceeded.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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").

  10. Time to first rescue medicine [ Time Frame: 24 hours ]
    Time to first intravenous and/or per oral rescue medicine.

  11. Total rescue analgesic consumption [ Time Frame: 24 hours ]
    Total intravenous and per oral rescue analgesic consumption over 24 hours.

  12. Respiratory depression [ Time Frame: 24 hours ]
    Continuous measurement of end-tidal carbon dioxide (ETCO2) with Smart CapnoLine® Plus (Microstream®), data are collected at postoperatively.

  13. Respiratory rate [ Time Frame: 24 hours ]
    Respiratory rate at rest is measured postoperatively.



Information from the National Library of Medicine

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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
Criteria

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.

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): NCT03314792


Locations
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Norway
Oslo University Hospital
Oslo, Norway, 0424
Sponsors and Collaborators
Oslo University Hospital
Investigators
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Principal Investigator: Harald Lenz, MD, PhD Oslo University Hospital
  Study Documents (Full-Text)

Documents provided by Harald Lenz, Oslo University Hospital:

Publications:

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Responsible Party: Harald Lenz, Principal investigator, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT03314792     History of Changes
Other Study ID Numbers: 2017/776
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: The database will be stored until 31.12.2035.
Access Criteria:

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.


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Harald Lenz, Oslo University Hospital:
pain
postoperative pain
postoperative pain management
opioid
analgesia
oxycodone
tapentadol
hysterectomy
respiratory depression

Additional relevant MeSH terms:
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Oxycodone
Pain, Postoperative
Acute Pain
Visceral Pain
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Signs and Symptoms
Nociceptive Pain
Tapentadol
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents