Effects of Tapentadol Versus Oxycodone After Hysterectomy.

NCT03314792 | Completed Phase 4

• 1 other identifier: 2017/776
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Postoperative; Pain Uterus; Pain, Acute; Opioid Use; Analgesics, Antipyretics, and Antirheumatics Causing Adverse Effects in Therapeutic Use; Visceral Pain

Keywords

pain; postoperative pain; postoperative pain management; opioid; analgesia; oxycodone; tapentadol; hysterectomy; respiratory depression

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Pain 2 hours postoperatively.

  2 hours

• Pain 3 hours postoperatively.

  3 hours

• Pain 24 hours postoperatively.

  24 hours

• Pain relief 30 minutes

  30 minutes

• Pain relief 1 hour

  1 hours

Study Arms (2)

Oxycodone

ACTIVE COMPARATOR

Active comparator drug administrated.

Drug: Oxycodone

Tapentadol

EXPERIMENTAL

Experimental drug administrated.

Drug: Tapentadol

Interventions

Tapentadol DRUG

* 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.

Tapentadol

Oxycodone DRUG

* 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.

Oxycodone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0424, Norway

Location

Related Publications (12)

• 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. doi: 10.1177/2049463716657363. Epub 2016 Jul 25.

  PMID: 27867511 BACKGROUND

• 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.

  PMID: 24437530 BACKGROUND

• Schroder 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.

  PMID: 20541444 BACKGROUND

• Riley J, Eisenberg E, Muller-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. doi: 10.1185/030079908x253708.

  PMID: 18039433 BACKGROUND

• 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.

  PMID: 19020157 BACKGROUND

• 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.

  PMID: 18851776 BACKGROUND

• Daniels SE, Upmalis D, Okamoto A, Lange C, Haeussler 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.

  PMID: 19203298 BACKGROUND

• 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.

  PMID: 19301989 BACKGROUND

• 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.

  PMID: 25536092 BACKGROUND

• 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.

  PMID: 20712805 BACKGROUND

• Ramaswamy S, Chang S, Mehta V. Tapentadol--the evidence so far. Anaesthesia. 2015 May;70(5):518-22. doi: 10.1111/anae.13080. No abstract available.

  PMID: 25866038 BACKGROUND

• Comelon M, Raeder J, Draegni T, Lieng M, Lenz H. Tapentadol versus oxycodone analgesia and side effects after laparoscopic hysterectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021 Sep 1;38(9):995-1002. doi: 10.1097/EJA.0000000000001425.

  PMID: 33428347 DERIVED

MeSH Terms

Conditions

Pain, Postoperative; Acute Pain; Visceral Pain; Pain; Agnosia; Respiratory Insufficiency

Interventions

Tapentadol; Oxycodone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms; Nociceptive Pain; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Harald Lenz, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: October 19, 2017
• Study Start: December 4, 2017
• Primary Completion: February 28, 2019
• Study Completion: February 28, 2019
• Last Updated: April 4, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

NO (1)