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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV Placebo 100 ml | Placebo Comparator | IV Placebo 100 ml dosed every every 6 hours for 24 hours (4 doses total). |
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| IV Placebo 65 ml | Placebo Comparator | IV Placebo 65 ml dosed every every 4 hours for 24 hours (6 doses total). |
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| IV Acetaminophen 1 gm | Experimental | IV Acetaminophen 1 gm dosed every every 6 hours for 24 hours (4 doses total). |
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| IV Acetaminophen 650 mg | Experimental | IV Acetaminophen 650 mg dosed every every 4 hours for 24 hours (6 doses total). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IV Placebo | Drug | IV, every 6 hours for 24 hours (4 doses total) |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to 24 hrs |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
Post Operative Exclusion Criteria
The Subject must not meet any of the following criteria prior to randomization to Study Medication:
Post Operative Day 1 Randomization Criterion On the morning of the first post operative day (POD1), the Subject must have a categorical pain intensity score at rest of moderate or severe and a score ≥ 40 mm and ≤ 70 mm at rest on a 100 mm Visual Analogue Scale (VAS)
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Helen Keller Hospital | Sheffield | Alabama | 35660 | United States | ||
| Precision Trials |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21353105 | Derived | Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB, Singla NK. A randomized, double-blind, placebo-controlled, multicenter, repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clin Ther. 2010 Dec;32(14):2348-69. doi: 10.1016/j.clinthera.2010.12.011. |
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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.
The study was conducted at 17 sites across the US from 27 Nov 2007 to 12 September 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intravenous (IV) Placebo (100 ml) | IV Placebo 100 ml dosed every every 6 hours for 24 hours (4 doses total). |
| FG001 | IV Acetaminophen 1 gm | IV Acetaminophen 1 gm dosed every every 6 hours for 24 hours (4 doses total). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| IV Placebo | Drug | IV, every 4 hours for 24 hours (6 doses total) |
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| IV Acetaminophen | Drug | IV, every 6 hours for 24 hours (4 doses total) |
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| IV Acetaminophen | Drug | IV, every 4 hours for 24 hours (6 doses total) |
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| Baseline to 24 hrs |
| 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). | First dose through 7 day follow up |
| 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:
| First dose to 30 days after last dose of study medication. |
| Phoenix |
| Arizona |
| 85032 |
| United States |
| Methodist Hospital | Arcadia | California | 91007 | United States |
| Glendale Adventist Medical Center | Glendale | California | 91206 | United States |
| Physicians Clinical Research Corporation | Laguna Hills | California | 92653 | United States |
| Huntington Memorial Hospital | Pasadena | California | 91105 | United States |
| Visions Clinical Research | Boynton Beach | Florida | 33414 | United States |
| Nature Coast Clinical Research | Crystal River | Florida | 34429 | United States |
| G and G Research, Inc. | Ft. Pierce | Florida | 34950 | United States |
| Advanced Surgery Associates at Mercy Hospital | Miami | Florida | 33133 | United States |
| University of Miami School of Medicine | Miami | Florida | 33136 | United States |
| William Beaumont Hospital (Royal Oak) | Royal Oak | Michigan | 48073 | United States |
| William Beaumont Hospital (Troy) | Royal Oak | Michigan | 48073 | United States |
| Cooper University Hospital | Camden | New Jersey | 08103 | United States |
| Staten Island University Hospital | Staten Island | New York | 10305 | United States |
| Memorial Herman/Memorial City Hospital | Houston | Texas | 77024 | United States |
| Texas Woman's Hospital | Houston | Texas | 77024 | United States |
| FG002 | IV Acetaminophen 650 mg | IV Acetaminophen 650 mg dosed every every 4 hours for 24 hours (6 doses total). |
| FG003 | IV Placebo (65 ml) | IV Placebo 65 ml dosed every every 4 hours for 24 hours (6 doses total). |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | IV Placebo | All subjects randomized to receive IV Placebo 100 ml and IV placebo 65 ml groups combined |
| BG001 | IV Acetaminophen 1 gm | All subjects randomized to receive IV Acetaminophen 1 gm |
| BG002 | IV Acetaminophen 650 mg | All subjects randomized to receive IV Acetaminophen 650 mg |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Units on a scale | Baseline to 24 hrs |
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| 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. | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Units on a scale | Baseline to 24 hrs |
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| 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). | All analyses of safety were conducted on the safety population, which included those subjects who received any portion of a dose of study medication. | Posted | Sep 2009 | Number | Subjects | First dose through 7 day follow up |
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| 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:
| All analyses were conducted on the safety population, which included those subjects who received any portion of a dose of study medication. | Posted | Sep 2009 | Number | Subjects | First dose to 30 days after last dose of study medication. |
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Adverse Events were collected from T0 (on or after start of study drug) to Day 7 after surgery. Serious Adverse Events were collected from T0 to 30 days after the last dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intravenous (IV) Placebo (100 ml) | IV Placebo 100 ml dosed every every 6 hours for 24 hours (4 doses total). | 0 | 43 | 12 | 43 | ||
| EG001 | IV Acetaminophen 1 gm | IV Acetaminophen 1 gm dosed every every 6 hours for 24 hours (4 doses total). | 1 | 91 | 42 | 91 | ||
| EG002 | IV Acetaminophen 650 mg | IV Acetaminophen 650 mg dosed every every 4 hours for 24 hours (6 doses total). | 3 | 43 | 16 | 43 | ||
| EG003 | IV Placebo (65 ml) | IV Placebo 65 ml dosed every every 4 hours for 24 hours (6 doses total). | 2 | 67 | 27 | 67 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Postoperative abscess | Infections and infestations | MedDRA (10.0) | Non-systematic Assessment |
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| Postoperative ileus | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA )10.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Infusion site pain | General disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Incision site pain | Injury, poisoning and procedural complications | MedDRA (10.0) | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (10.0) | Non-systematic Assessment |
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| Dypsnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Non-systematic Assessment |
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One subject was randomized to receive IV APAP 1 g, but was administered IV APAP 650 mg. The subject was included in 1g IV APAP group for efficacy purposes and included in IV APAP 650 mg safety group for AE purposes.
Institution or Investigator may publish the results of the study (without raw data, detailed patient Case Report Forms, or patient identification) only after such cooperative publication, or 18 months after Cadence's final evaluation of all study data from all sites, whichever occurs first. At least 60 days prior to submission, or prior to any public presentation, a copy of the abstract, manuscript or presentation will be provided to Cadence who will have 60 days to respond with comments.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lawrence Hill | Mallinckrodt Pharmaceuticals | 908-238-6370 | lawrence.hill@mallinckrodt.com |
| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000082 | Acetaminophen |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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