Hysterectomy, Postoperative Pain
Conditions
Keywords
Pain, Gynecologic, IV Acetaminophen, Postoperative, Analgesic
Brief summary
This study will be investigating the efficacy and safety administration of multiple doses of intravenous (IV) acetaminophen (IVAPAP) in the 48 hour period following Gynecologic Surgery.
Detailed description
The research hypothesis is that IV Acetaminophen will provide greater reduction in pain intensity and greater pain relief for moderate and severe pain as compared to placebo in the 48 hours following surgery.
Interventions
DRUGIV Acetaminophen
Intravenous acetaminophen 1 g/100 mL
DRUGIV Placebo 100 mL solution
IV Placebo 100 mL solution dosed at same frequency as IV Acetaminophen every 6 hours (q6h)
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Undergo gynecologic surgery using standard abdominal approach such as midline or Pfannenstiel incision * 18-75 years of age * Body Mass Index (BMI) between 19-45 * American Society of Anesthesiologists (ASA) risk class of I, II, III * Not have received neuraxial (spinal or epidural) opioid analgesics prior to or during surgery * Moderate to Severe pain at rest
Exclusion criteria
* Requires any additional surgical procedures either related or unrelated to gynecologic surgery during same hospitalization * Procedures involving only minimal incisions such as laparotomy, laparoscopy, supraumbilical or Maylard incisions * Has know hypersensitivity to opioids, acetaminophen, or the excipients of IV acetaminophen * Known history of alcohol or drug abuse or misuse * Has impaired liver function Aspartate transaminase(AST), Alanine aminotransferase(ALT), bilirubin greater than or equal to 2 times upper limit of normal * Has significant medical disease(s), or conditions that may contraindicate participation in the study * Has participated in another clinical trial within 30 days of surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity at Rest-Baseline to 24 Hours (SPI24rest), 1 Gram IV Acetaminophen vs. Placebo. | Baseline (just prior to the first dose) through 24 hours | The Sum of Pain Intensity (SPI) score incorporates the analgesic effects on pain intensity (PI) from Baseline to 24 hours. SPI was measured by the 100 millimeter (mm) long Visual Analog Scale (VAS) over 24 hours after treatment. Subjects were asked to mark the level of pain they were experiencing at a certain timepoint on the scale The 100mm VAS scale was used with the left terminus (0 mm) of the scale No Pain and the right terminus (100 mm) with Worst Pain Imaginable. The range of measurement is 0-2400 mm for 24 hours. |
| Sum Pain Intensity at Rest-Baseline to 48 Hours (SPI48rest), 1 Gram IV Acetaminophen vs. Placebo | Baseline (just prior to the first dose) through 48 hours | The Sum of Pain Intensity (SPI) score incorporates the analgesic effects on pain intensity (PI) from Baseline to 48 hours. SPI was measured by the 100 millimeter (mm) long Visual Analog Scale (VAS) over 48 hours after treatment. Subjects were asked to mark the level of pain they were experiencing at a certain timepoint on the scale The 100 mm VAS scale was used with the left terminus (0 mm) of the scale No Pain and the right terminus (100 mm) with Worst Pain Imaginable. The range of measurement is 0-4800 mm for 48 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 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 administration of the first dose of study medication (T0) |
| Subjects Who Experienced at Least One Treatment-emergent Serious Adverse Event. | 32 days following first dose of study medication. | Number of subjects who reported SAEs during the study. A serious Adverse event (SAE) is defined as any untoward medical occurence at any dose of 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, or Is an important medical event |
Countries
United States
Participant flow
Recruitment details
Gynecologists and/or anesthesiologists were selected to participate as Principal Investigators.
Pre-assignment details
Subjects were required to meet eligibility criteria prior to surgery and then again had to meet post surgical inclusion criteria.Subjects had to achieve a sufficient pain intensity score prior to entering the study.
Participants by arm
| Arm | Count |
|---|---|
| IV Acetaminophen 1 g/100 mL Solution All subjects randomized to receive Intravenous (IV) Acetaminophen 1 g/100 mL solution every 6 hours for 48 hours for a total of 8 doses. | 166 |
| IV Placebo 100 mL Solution All subjects randomized to receive Intravenous (IV) placebo 100 mL solution every 6 hours for 48 hours for a total of 8 doses. | 165 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol non-compliance | 2 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | IV Acetaminophen 1 g/100 mL Solution | IV Placebo 100 mL Solution | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 163 Participants | 161 Participants | 324 Participants |
| Region of Enrollment United States | 166 participants | 165 participants | 331 participants |
| Sex: Female, Male Female | 166 Participants | 165 Participants | 331 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 135 / 166 | 145 / 165 |
| serious Total, serious adverse events | 11 / 166 | 14 / 165 |
Outcome results
Primary
Sum of Pain Intensity at Rest-Baseline to 24 Hours (SPI24rest), 1 Gram IV Acetaminophen vs. Placebo.
The Sum of Pain Intensity (SPI) score incorporates the analgesic effects on pain intensity (PI) from Baseline to 24 hours. SPI was measured by the 100 millimeter (mm) long Visual Analog Scale (VAS) over 24 hours after treatment. Subjects were asked to mark the level of pain they were experiencing at a certain timepoint on the scale The 100mm VAS scale was used with the left terminus (0 mm) of the scale No Pain and the right terminus (100 mm) with Worst Pain Imaginable. The range of measurement is 0-2400 mm for 24 hours.
Time frame: Baseline (just prior to the first dose) through 24 hours
Population: All efficacy analyses were conducted using the mITT population, defined as those subjects who received a complete dose of study medication prior to a request for rescue medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen 1 g/100 ml Solution | Sum of Pain Intensity at Rest-Baseline to 24 Hours (SPI24rest), 1 Gram IV Acetaminophen vs. Placebo. | 1793.3 units on a scale (in millimeters) | Standard Deviation 481.49 |
| IV Placebo 100 ml Solution | Sum of Pain Intensity at Rest-Baseline to 24 Hours (SPI24rest), 1 Gram IV Acetaminophen vs. Placebo. | 1845.3 units on a scale (in millimeters) | Standard Deviation 420.21 |
Primary
Sum Pain Intensity at Rest-Baseline to 48 Hours (SPI48rest), 1 Gram IV Acetaminophen vs. Placebo
The Sum of Pain Intensity (SPI) score incorporates the analgesic effects on pain intensity (PI) from Baseline to 48 hours. SPI was measured by the 100 millimeter (mm) long Visual Analog Scale (VAS) over 48 hours after treatment. Subjects were asked to mark the level of pain they were experiencing at a certain timepoint on the scale The 100 mm VAS scale was used with the left terminus (0 mm) of the scale No Pain and the right terminus (100 mm) with Worst Pain Imaginable. The range of measurement is 0-4800 mm for 48 hours.
Time frame: Baseline (just prior to the first dose) through 48 hours
Population: All efficacy analyses were conducted using the mITT population, defined as those subjects who received a complete dose of study medication prior to a request for rescue medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen 1 g/100 ml Solution | Sum Pain Intensity at Rest-Baseline to 48 Hours (SPI48rest), 1 Gram IV Acetaminophen vs. Placebo | 3612.4 units on a scale (in millimeters) | Standard Deviation 966.66 |
| IV Placebo 100 ml Solution | Sum Pain Intensity at Rest-Baseline to 48 Hours (SPI48rest), 1 Gram IV Acetaminophen vs. Placebo | 3718.2 units on a scale (in millimeters) | Standard Deviation 829.21 |
Secondary
Subjects Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
Number of subjects who experienced at least one treatment emergent adverse event (TEAE) A TEAE is an adverse event that occurs on or after administration of 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 Acetaminophen 1 g/100 ml Solution | Subjects Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 141 Subjects |
| IV Placebo 100 ml Solution | Subjects Who Experienced at Least One Treatment-emergent Adverse Event (TEAE) | 149 Subjects |
Secondary
Subjects Who Experienced at Least One Treatment-emergent Serious Adverse Event.
Number of subjects who reported SAEs during the study. A serious Adverse event (SAE) is defined as any untoward medical occurence at any dose of 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, or Is an important medical event
Time frame: 32 days following first dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Acetaminophen 1 g/100 ml Solution | Subjects Who Experienced at Least One Treatment-emergent Serious Adverse Event. | 11 Subjects |
| IV Placebo 100 ml Solution | Subjects Who Experienced at Least One Treatment-emergent Serious Adverse Event. | 14 Subjects |