Pain
Conditions
Keywords
Abdominal Laparoscopic Surgery
Brief summary
This research study will look at the pain relieving ability and safety of using repeated doses of intravenous (into the vein \[IV\]) acetaminophen in the treatment of moderate postoperative pain after planned or elective abdominal laparoscopic surgery, such as a laparoscopic abdominal hysterectomy or laparoscopic cholecystectomy (removal of the gall bladder).
Detailed description
To assess the analgesic efficacy of repeated doses of intravenous acetaminophen (IV APAP) versus Placebo in the treatment of moderate postoperative pain after abdominal laparoscopic surgery.
Interventions
DRUGIV Placebo
IV, every 6 hours for 24 hours (4 doses total)
DRUGIV Acetaminophen
IV, every 6 hours for 24 hours (4 doses total)
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Provide written Informed Consent prior to participation in the Study * Is scheduled to undergo abdominal laparoscopic surgery under general anesthesia (laparoscopic bariatric procedures, including gastric bypass or gastric banding, laparoscopic exploratory procedures in which no visceral dissection is performed, and laparoscopic procedures with minimal visceral dissection, such as laparoscopic sterilization,are excluded) * If Subject is a female of childbearing potential, have a negative pregnancy test within 21 days of surgery * Be at least 18, but not more than 80 years of age * Have a Body Mass Index (BMI) ≥ 19 and ≤ 40 lb/in2 * Have an American Society of Anesthesiologist (ASA) risk class of I, II, or III * Have the ability to read and understand the Study procedures and the use of the pain scales and have the ability to communicate meaningfully with the Study Investigator and staff * Be free of other physical, mental, or medical conditions which, in the opinion of the Investigator, makes Study participation inadvisable
Exclusion criteria
* Used opioids or tramadol daily for greater than 7 days prior to Study Medication administration (Subjects who, in the Investigator's opinion have or are developing opioid tolerance are to be excluded) * Has been treated with Chapparal, Comfrey, Germander, Gin Bu Huan, Kava, Pennyroyal, Skullcap, St. John's Wort, or Valerian within 14 days prior to surgery * Has significant medical disease(s), laboratory abnormalities or condition(s) that in the Investigator's judgment could compromise the Subject's welfare, ability to communicate with the Study staff, complete Study activities, or would otherwise contraindicate Study participation * Has known hypersensitivity to opioids, acetaminophen, or the inactive ingredients (excipients) of the Study Medication * Has known or suspected history of alcohol or drug abuse or dependence within the previous 2 years * Has impaired liver function, e.g., aspartate aminotransferase (AST)/Alanine transaminase (ALT)/bilirubin greater than or equal to 3.0 times the upper limit of normal, active hepatic disease, evidence of clinically significant liver disease, or other condition (e.g., alcoholism, cirrhosis, or hepatitis) that may suggest the potential for an increased susceptibility to hepatic toxicity with Study Medication exposure * Has been treated with monoamine oxidase inhibitors (MAOIs) within 7 days prior to surgery * Has participated in another clinical Study (investigational or marketed product) within 30 days of surgery Post Operative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 1 g IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | Baseline to 24 hrs | Pain Intensity (PI) as measured by a 100 millimeter (mm) long Visual Analogue Scale (VAS) over 24 hours after treatment minus the Baseline VAS score. The 100 mm VAS was drawn on a pain ruler and labeled at its left end with '0 = No Pain' and with 100 = Worst Pain Imaginable' at its right end. Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI at baseline was compared to the PI at each timepoint and differences were summed over the 24 hour time period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 650 mg IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | Baseline to 24 hrs | Sum of Pain Intensity (PI) as measured by the 100 mm long Visual Analogue Scale (VAS) over 24 hours after treatment subtracting the Baseline VAS score.The 100 mm VAS was drawn on a pain ruler and labeled at it's left end with 0 = No Pain' and its right end with '100 = Worst Pain Imaginable.' Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI difference from baseline was calculated at each assessment over a 24 hour period. |
| The Number of Subjects Reporting a Treatment Emergent Adverse Event | First dose through 7 day follow up | Number of subjects who experienced at least one treatment emergent adverse event (TEAE). A TEAE is an adverse event that occurs on or after the first dose of study medication (T0). |
| The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event | First dose to 30 days after last dose of study medication. | The number of subjects who reported at least one treatment emergent SAE during the study. A Serious Adverse Event is defined as any untoward medical occurrence at any dose of blinded study medication that: * results in death * is life-threatening * requires inpatient hospitalization or causes prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * is an important medical event |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 17 sites across the US from 27 Nov 2007 to 12 September 2008.
Pre-assignment details
On the morning of Post Operative Day 1, the subject was to have a pain intensity (PI) categorical score of moderate or severe and a visual analog scale (VAS) \>= 40 mm, but \<= 70 mm at rest on a 100 mm VAS.
Participants by arm
| Arm | Count |
|---|---|
| IV Placebo All subjects randomized to receive IV Placebo 100 ml and IV placebo 65 ml groups combined | 110 |
| IV Acetaminophen 1 gm All subjects randomized to receive IV Acetaminophen 1 gm | 92 |
| IV Acetaminophen 650 mg All subjects randomized to receive IV Acetaminophen 650 mg | 42 |
| Total | 244 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 | 2 | 2 |
| Overall Study | Subject refused to have blood drawn | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | IV Placebo | IV Acetaminophen 1 gm | IV Acetaminophen 650 mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 6 Participants | 4 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants | 86 Participants | 38 Participants | 224 Participants |
| Sex: Female, Male Female | 91 Participants | 74 Participants | 33 Participants | 198 Participants |
| Sex: Female, Male Male | 19 Participants | 18 Participants | 9 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 43 | 42 / 91 | 16 / 43 | 27 / 67 |
| serious Total, serious adverse events | 0 / 43 | 1 / 91 | 3 / 43 | 2 / 67 |
Outcome results
Primary
Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 1 g IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.)
Pain Intensity (PI) as measured by a 100 millimeter (mm) long Visual Analogue Scale (VAS) over 24 hours after treatment minus the Baseline VAS score. The 100 mm VAS was drawn on a pain ruler and labeled at its left end with '0 = No Pain' and with 100 = Worst Pain Imaginable' at its right end. Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI at baseline was compared to the PI at each timepoint and differences were summed over the 24 hour time period.
Time frame: Baseline to 24 hrs
Population: All efficacy analyses were conducted using the modified intent-to-treat (mITT) population, defined as those subjects who received at least one complete infusion of study medication prior to requesting rescue medication.Worst Observation Carried Forward (WOCF) imputation was applied after first rescue medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Placebo | Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 1 g IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | -45.2 Units on a scale | Standard Deviation 513.25 |
| IV Acetaminophen 1 gm | Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 1 g IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | -194.1 Units on a scale | Standard Deviation 593.62 |
Secondary
Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 650 mg IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.)
Sum of Pain Intensity (PI) as measured by the 100 mm long Visual Analogue Scale (VAS) over 24 hours after treatment subtracting the Baseline VAS score.The 100 mm VAS was drawn on a pain ruler and labeled at it's left end with 0 = No Pain' and its right end with '100 = Worst Pain Imaginable.' Subjects placed a mark on the scale to represent their perceived pain. The score was the distance in mm from the left end of the VAS to the point where the subject's mark crossed the line. PI difference from baseline was calculated at each assessment over a 24 hour period.
Time frame: Baseline to 24 hrs
Population: Included modified Intent To Treat group (mITT), defined as randomized subjects who received at least one complete infusion of study medication prior to receiving rescue medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Placebo | Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 650 mg IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | -45.2 Units on a scale | Standard Deviation 513.25 |
| IV Acetaminophen 1 gm | Sum Pain Intensity Difference - Baseline to 24 Hours (SPID24), 650 mg IV Acetaminophen vs. Placebo (PI Was Measured at the Timepoints of T0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, and 24 Hours.) | -323.1 Units on a scale | Standard Deviation 619.27 |
Secondary
The Number of Subjects Reporting a Treatment Emergent Adverse Event
Number of subjects who experienced at least one treatment emergent adverse event (TEAE). A TEAE is an adverse event that occurs on or after the first dose of study medication (T0).
Time frame: First dose through 7 day follow up
Population: All analyses of safety were conducted on the safety population, which included those subjects who received any portion of a dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Placebo | The Number of Subjects Reporting a Treatment Emergent Adverse Event | 68 Subjects |
| IV Acetaminophen 1 gm | The Number of Subjects Reporting a Treatment Emergent Adverse Event | 65 Subjects |
| IV Acetaminophen 650 mg | The Number of Subjects Reporting a Treatment Emergent Adverse Event | 28 Subjects |
Secondary
The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event
The number of subjects who reported at least one treatment emergent SAE during the study. A Serious Adverse Event is defined as any untoward medical occurrence at any dose of blinded study medication that: * results in death * is life-threatening * requires inpatient hospitalization or causes prolongation of existing hospitalization * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * is an important medical event
Time frame: First dose to 30 days after last dose of study medication.
Population: All analyses were conducted on the safety population, which included those subjects who received any portion of a dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Placebo | The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event | 2 Subjects |
| IV Acetaminophen 1 gm | The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event | 1 Subjects |
| IV Acetaminophen 650 mg | The Number of Subjects Reporting a Treatment Emergent Serious Adverse Event | 3 Subjects |