Trial Outcomes & Findings for Efficacy and Safety of Intravenous Acetaminophen Over 48 Hrs for the Treatment of Post-op Pain After Gynecologic Surgery (NCT NCT00399568)

Last Updated: 2016-10-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

331 participants

Primary outcome timeframe

Baseline (just prior to the first dose) through 24 hours

Results posted on

2016-10-21

Participant Flow

Gynecologists and/or anesthesiologists were selected to participate as Principal Investigators.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	166	165
Overall Study COMPLETED	154	156
Overall Study NOT COMPLETED	12	9

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	7	3
Overall Study Protocol non-compliance	2	2
Overall Study Lost to Follow-up	2	2

Baseline Characteristics

Efficacy and Safety of Intravenous Acetaminophen Over 48 Hrs for the Treatment of Post-op Pain After Gynecologic Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV Acetaminophen 1 g/100 mL Solution n=166 Participants 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.	IV Placebo 100 mL Solution n=165 Participants All subjects randomized to receive Intravenous (IV) placebo 100 mL solution every 6 hours for 48 hours for a total of 8 doses.	Total n=331 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	163 Participants n=5 Participants	161 Participants n=7 Participants	324 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	166 Participants n=5 Participants	165 Participants n=7 Participants	331 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	166 participants n=5 Participants	165 participants n=7 Participants	331 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	IV Acetaminophen 1 g/100 ml Solution n=162 Participants mITT Population IV acetaminophen 1 g/100 ml Solution	IV Placebo 100 ml Solution n=159 Participants mITT Population IV Placebo 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	1845.3 units on a scale (in millimeters) Standard Deviation 420.21

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	IV Acetaminophen 1 g/100 ml Solution n=162 Participants mITT Population IV acetaminophen 1 g/100 ml Solution	IV Placebo 100 ml Solution n=159 Participants mITT Population IV Placebo 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	3718.2 units on a scale (in millimeters) Standard Deviation 829.21

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome measures
Measure	IV Acetaminophen 1 g/100 ml Solution n=166 Participants mITT Population IV acetaminophen 1 g/100 ml Solution	IV Placebo 100 ml Solution n=165 Participants mITT Population IV Placebo 100 ml solution
Subjects Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	141 Subjects	149 Subjects

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	IV Acetaminophen 1 g/100 ml Solution n=162 Participants mITT Population IV acetaminophen 1 g/100 ml Solution	IV Placebo 100 ml Solution n=159 Participants mITT Population IV Placebo 100 ml solution
Subjects Who Experienced at Least One Treatment-emergent Serious Adverse Event.	11 Subjects	14 Subjects

Adverse Events

IV Acetaminophen 1g/100 mL Solution

Serious events: 11 serious events

Other events: 135 other events

Deaths: 0 deaths

IV Placebo 100 mL Solution

Serious events: 14 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IV Acetaminophen 1g/100 mL Solution n=166 participants at risk Safety Population (defined as those subjects who received any portion of a dose of IV acetaminophen 1g/100 mL solution)	IV Placebo 100 mL Solution n=165 participants at risk Safety Population (defined as those subjects who received any portion of a dose of IV Placebo 100 mL solution)
Blood and lymphatic system disorders Anaemia	7.8% 13/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	6.7% 11/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Cardiac disorders Tachycardia	4.8% 8/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	7.9% 13/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Abdominal distension	5.4% 9/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	4.8% 8/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Constipation	28.9% 48/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	29.7% 49/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Flatulence	12.7% 21/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	17.0% 28/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Nausea	57.8% 96/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	53.3% 88/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Vomiting	22.3% 37/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	17.0% 28/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
General disorders Pyrexia	11.4% 19/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	22.4% 37/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Nervous system disorders Dizziness	6.0% 10/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	9.7% 16/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Nervous system disorders Headache	13.3% 22/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	10.3% 17/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Psychiatric disorders Insomnia	10.8% 18/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	6.1% 10/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Skin and subcutaneous tissue disorders Pruritis	14.5% 24/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	12.7% 21/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Musculoskeletal and connective tissue disorders Back Pain	1.8% 3/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	5.5% 9/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication

Additional Information

Lawrence Hill

Mallinckrodt Pharmaceuticals

Phone: 908-238-6370

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigator may publish only after cooperative publication or 18 months after sponsor's final evaluation of study data, whichever occurs first. At least 60 days prior to submission for publication, investigator must submit manuscript to sponsor for review and comment. Sponsor has 60 day period thereafter to respond with comment. Investigator will remove confidential information at the request of sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	IV Acetaminophen 1g/100 mL Solution n=166 participants at risk Safety Population (defined as those subjects who received any portion of a dose of IV acetaminophen 1g/100 mL solution)	IV Placebo 100 mL Solution n=165 participants at risk Safety Population (defined as those subjects who received any portion of a dose of IV Placebo 100 mL solution)
Blood and lymphatic system disorders Neutropenia	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Abdominal pain lower	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Ileus	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	1.2% 2/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Gastrointestinal disorders Small intestinal obstruction	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
General disorders Pyrexia	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Infections and infestations Abdominal abscess	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Infections and infestations Pelvic abscess	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	1.2% 2/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Infections and infestations Vaginal infection	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Injury, poisoning and procedural complications Accidental overdose	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	3.0% 5/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Injury, poisoning and procedural complications Seroma	1.2% 2/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Metabolism and nutrition disorders Diabetic ketoacidosis	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Vascular disorders Aneurysm	0.60% 1/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.00% 0/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Vascular disorders Deep vein thrombosis	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication
Vascular disorders Haemorrhage	0.00% 0/166 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication	0.61% 1/165 • Adverse Events were reported from the start of study medication until the follow up visit on Day 7 (+/- 2 days). Serious Adverse Events were collected for 32 days following start of study medication