An Efficacy and Safety Study to Compare Fentanyl Ionsys and Routine Care With Intravenous (IV) Morphine Patient-controlled Analgesia (PCA) in Participants Who Have Undergone Elective Major Abdominal or Orthopedic Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the mobilization characteristics, clinical use, safety and Ease of Care (EOC) of a fentanyl Iontophoretic Transdermal Patient Controlled Analgesia (PCA) system (Ionsys) and morphine intravenous (IV) PCA for management of moderate (medium level of seriousness) to severe (very serious) acute (a quick and severe) pain in participants who have undergone elective major abdominal or orthopedic (pertaining to the bones) surgery.

Detailed Description
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This is a randomized (study drug assigned by chance), multicentre (when more than one hospital or medical school team work on a medical research study), open-label (participants and physicians are told which treatment the participants are receiving), active-controlled (experimental treatment is compared to a standard treatment), parallel group study (a study comparing the response in two or more groups of participants receiving different treatments). The study will consist of 2 phases: screening phase and an open-label treatment phase. The duration of participation in the study for an individual participant will be 72 hours. Eligible participants (who require pain treatment with strong opioids [morphine like medications] for at least 24 hours after an elective spine or elective orthopedic surgery) will be randomly assigned to receive either Ionsys or morphine IV PCA. Participants' safety will be monitored.

Official Title
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Comparison of Ionsys and Routine Care With Morphine IV (Intravenous) PCA in the Management of Early Post-operative Mobilisation, Ability to Mobilise and in Time to Fitness For Discharge

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Device: Fentanyl IONSYS
* Device: Morphine IV PCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants, after an elective major abdominal or orthopedic (pertaining to bones) surgery Expected to have acute (a quick and severe form of illness in its early stage) moderate (medium level of seriousness) to severe (very serious) post-operative pain requiring parenteral (administration by injection) opioids (morphine like medication) for at least 24 hours after surgery Participants who have undergone General anesthesia (loss of sensation or feeling), spinal anesthesia of less than or equal to 4 hours duration or epidural (outside the spinal cord) anesthesia Participants with respiratory rate 10 to 24 breaths per minute Participants with a pain score less than or equal to 4 out of 10 on a Numerical Rating Scale (NRS), after titration to comfort with intravenous (IV) morphine Exclusion Criteria Surgery secondary to malignancy (cancer or other progressively enlarging and spreading tumor) or trauma (injury) History of psychological opioid dependence and/or known or suspected to be opioid dependent Severe chronic (lasting a long time) obstructive respiratory symptoms susceptibility to respiratory depression, moderate to severe renal (having to do with the kidney) dysfunction Peri-operative administration of opioids other than morphine, fentanyl, sufentanil, alfentanil or remifentanil Require high doses of opioids to control their pain (more than 40 milligram morphine IV) during titration to comfort, or more than 6 hours have elapsed since the participant arrived in the recovery room or Monoamine oxidase inhibitors (MAOI) within 14 days pre-study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl IONSYS<br>Participants will receive 40 microgram (mcg) of fentanyl dose up to a maximum of 240 mcg (6 doses each of 10 minutes duration) per hour but not more than a maximum of 80 doses within a 24 hour period from an Iontophoretic Transdermal System (IONSYS). | Device: Fentanyl IONSYS<br>* Participants will receive 40 mcg of fentanyl dose up to a maximum of 240mcg (6 doses each of 10 minutes duration) per hour but not more than a maximum of 80 doses within a 24 hour period from an Iontophoretic Transdermal System (IONSYS).<br>|
| Active Comparator: Morphine IV PCA<br>Morphine sulphate solution will be administered intravenously (directly into the vein, IV) by a patient-controlled analgesia (PCA) pump using set bolus (a large amount) doses with a fixed lock out period as per physician's discretion (maximum total dose of 20 milligram per 2 hours) for 72 hours. | Device: Morphine IV PCA<br>* Morphine sulphate solution will be administered intravenously (IV) by a patient-controlled analgesia (PCA) pump using set bolus doses with a fixed lock out period as per physician's discretion (maximum total dose of 20 milligram per 2 hours) for 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant's Evaluation of Mean Ability to Mobilize After Surgery | The ability to mobilize was assessed through a combined analysis of participant's responses to the following 3 questions: 1-Because of the system/device, I had to be careful when I used my hands; 2-The system/device made it difficult for me to adjust my position in bed; 3-The system/device interfered with my ability to get out of bed and walk around. All 3 items were scored on a 6-point Likert scale, ranging from not at all (score 0) to a very great deal (score 5). Total ability to mobilize was assessed as average of 3 scores which range from 0 (best mobility) to 5 (worst mobility). | Hour 72 or early study withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Numerical Rating Scale (NRS) | Pain intensity NRS measured pain intensity experienced by the participant on a scale, 0 to 10, where 0 means no pain and 10 mean the worst possible pain. Participant's pain intensity was assessed by asking following question to the participant: on a scale 0 to 10 where 0 means no pain, and 10 means the worst possible pain, rate the pain that you have now. | Baseline, Hour 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, study treatment discontinuation or withdrawal, and when participant was fit for discharge (FFD) (assessed up to 91 hours) | 
| Nurse Ease of Care (EOC) Questionnaire Score | Nurse EOC questionnaire had 22 items and covered 3 aspects of care delivery associated with acute care pain management systems: time, bothersome and satisfaction. Items were scored on a 6-point Likert scale, ranging from 'not at all' (Score 0) to 'a very great deal' (score 5). The total score was calculated as the mean of the non-missing items for all the questions. | When participant was fit for discharge (FFD) (assessed up to 91 hours) | 
| Number of Participants With Patient Global Assessment (PGA) of Method of Pain Control | The assessment consist of a categorical evaluation (poor, fair, good or excellent) of the method of pain control by asking following question from the participant: Overall, would you rate this PCA (participant controlled analgesia) method of pain control as being poor, fair, good, or excellent? | Hour 72 or early study withdrawal | 
| Time to Fit For Discharge (FFD) | Participants were assessed for fulfilling the following FFD criteria: 1- Retaining fluids and food; 2- Passing urine without the aid of a catheter; 3- Bowel sounds and/or opening; 4- Cardiovascular stability; 5- Respiratory stability; 6- No post-operative wound complications; 7- Pain adequately controlled with oral analgesia only; 8- Adequately mobile according to locally acceptable standards for mobility for surgery type and pre-operative expectations. The FFD criteria were answered on a Yes or No basis. When all criteria were answered as Yes, participant was considered to be FFD. | When participant was FFD (assessed up to 91 hours) | 
| Number of Participants Who Require Rescue Medication | Rescue medication was defined as a fast-acting medication given besides the study drug that could alleviate pain quickly, but the effects were not long lasting. Morphine was given intravenously as rescue medication for all participants randomly assigned to either treatment group. | Baseline up to Hour 3 | 
| Number of Participants Who Require Concomitant Antiemetic Medication | Antiemetic medicines are the drugs which prevent vomiting. | Baseline up to end of study treatment (Hour 72) | 
| Number of Participants Who Require Concomitant Non-opioid Analgesics | Non-opioid analgesics are non morphine like medications used to get relieve from pain. | Baseline up to end of study treatment (Hour 72) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCA, IONSYS, Fentanyl, Morphine, Postoperative pain, Mobilization