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CompletedNCT03365622Updated Jun 29, 2025Results posted

Efficacy of IV Acetaminophen Versus Oral Acetaminophen

A Phase 4 interventional study of acetaminophen and Acetaminophen in Nephrectomy, sponsored by University of Rochester. Completed at 1 site in United States. Open to participants aged 18 Years to 89 Years. Per ClinicalTrials.gov, last updated 2025-06-29.

Sponsored by University of Rochester · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
214
Allocation
Randomized
Ages
18 Years to 89 Years
Sex
All
01

Study summary

The aim of this study is to determine whether intravenous acetaminophen compared to enteric acetaminophen offers increased efficacy in patients who are scheduled for laparoscopic donor nephrectomy and for patients scheduled for robot-assisted, laparoscopic nephrectomy for cancer at the University of Rochester Medical Center. The standard surgical and post-operative care, including post-operative pain management will not be altered.

02

Conditions studied

  • Nephrectomy
03

Who can participate

Ages eligible
18 Years to 89 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Be at least 18 years old
  • Be scheduled for donor nephrectomy or robot-assisted, laparoscopic nephrectomy for cancer at University of Rochester Medical Center
  • Have cognitive ability to verbally rate their pain on the Numeric Rating Scale (NRS).

Exclusion criteria

Exclusion Criteria:

  • Age younger than 18 years old or older than 90 years old
  • Pregnancy (Pre-operative pregnancy test is standard of care for all elective operating room cases)
  • Weight less than 50 kg
  • Epidural use
  • History of known liver disease.
  • Patient unable to take enteral medications.
  • Be taking opioid medications chronically.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
214 participants (actual)

Study arms

  • Active comparator
    IV acetaminophen and placebo pills

    Drug: acetaminophen · Drug: Placebo Oral Tablet

  • Placebo comparator
    placebo IV (normal saline) + oral acetaminophen

    Drug: Acetaminophen · Drug: Placebos

Interventions

  • Drugacetaminophen

    Active Intravenous doses will consist of a single 1,000mg/100 ml IV dose with contents of commercial vials transferred to an empty sterile IV bag.

  • DrugAcetaminophen

    500mg acetaminophen tablet ,2 capsules oral every six hours for 24 hours

  • DrugPlacebos

    Placebo Intravenous doses will consist of 100ml of normal saline transferred to an empty sterile IV bag.

  • DrugPlacebo Oral Tablet

    Placebo, opaque capsules that have been filled with inert powder (lactose USP), 2 capsules oral every six hours for 24 hours

05

What researchers measure

Primary outcomes

  1. Total Opioid Dose (MME) Used in 24 Hours

    Total opiate dose used from the study start (when the first dose of acetaminophen is administered in the pre-anesthesia holding area) to 24 hours post-operatively (in morphine milligram equivalents (MME)).This will include opiates administered intra-operatively.

    Time frame: 20 to 24 hours post-operatively

Secondary outcomes

  1. Average Surgical Pain Intensity

    Average surgical pain intensity on a 0-10 numeric rating scale (NRS) administered between 20 and 24 hours post-operatively, with gatekeeping used to control for multiplicity. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

    Time frame: 20-24 hours post-operatively

  2. Average Surgical Pain Intensity

    Average surgical pain intensity on a 0-10 numeric rating scale (NRS) administered between 20 and 24 hours post-operatively, with gatekeeping used to control for multiplicity. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

    Time frame: 1-2 hours post-operatively

  3. Mean Inspiratory Capacity

    The mean inspiratory capacity is presented as a percentage of the subject's baseline (pre-operative) inspiratory capacity, recorded at the time of pain intensity assessments between 1-2 hours postoperatively. Inspiratory capacity is measured using a Voldyne 5000 incentive spirometer (Hudson RCI, Teleflex Medical) and recorded in milliliters to the nearest 250 cc mark on the incentive spirometer. Higher percentages reflect better recovery of inspiratory function.

    Time frame: 1-2 hours post-operatively

  4. Mean Inspiratory Capacity

    The mean inspiratory capacity is presented as a percentage of the subject's baseline (pre-operative) inspiratory capacity, recorded at the time of pain intensity assessments between 20-24 hours postoperatively. Inspiratory capacity is measured using a Voldyne 5000 incentive spirometer (Hudson RCI, Teleflex Medical) and recorded in milliliters to the nearest 250 cc mark on the incentive spirometer. Higher percentages reflect better recovery of inspiratory function.

    Time frame: 20-24 hours post-operatively

  5. Dynamic Pain Score During Incentive Spirometer Use

    Dynamic pain score on a 0-10 numeric rating scale (NRS) with incentive spirometer use taken during pain intensity assessments at 1-2 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

    Time frame: 1-2 hours post-operatively

  6. Dynamic Pain Score During Incentive Spirometer Use

    Dynamic pain score on a 0-10 numeric rating scale (NRS) with incentive spirometer use taken during pain intensity assessments at 20-24 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

    Time frame: 20-24 hours post-operatively

  7. Surgical Pain Score During the 20-24 Hour Assessment

    Pain intensity on a 0-10 numeric rating scale (NRS) prior to incentive spirometry use was taken during pain intensity assessments at 20-24 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

    Time frame: 20-24 hours post-operatively

  8. Time to First Narcotic Use

    Time to first postoperative narcotic use, measured in hours (range: 1 to 24).

    Time frame: 24 hours post-operatively

  9. Number of Participants With Nausea

    Number of participants with nausea was assessed based on the administration of anti-emetic medications, with a value of 0 indicating no nausea and 1 indicating the presence of nausea.

    Time frame: 24 hours post-operatively

  10. Time to Discharge From Post-anesthesia Care Unit

    Length of time in minutes from PACU(post-anesthesia care unit) arrival to discharge.

    Time frame: 24 hours

  11. Time to Hospital Discharge

    Number of days to discharge from hospital

    Time frame: 30 days

06

Results

Posted Jun 29, 2025
Limitations and caveats
The main limitation was the addition of TAP blocks mid-study for laparoscopic nephrectomy patients. This change likely didn't affect results, as both groups had similar exposure. Variability in gastric drainage, delayed PACU dosing due to lethargy, and prolonged procedures may have influenced outcomes. Lastly, no control group without acetaminophen was included due to ethical concerns over withholding standard pain management.

Participant flow

Adult patients 18 years to 90 years old with the cognitive ability to rate their pain on the Numeric Rating Scale (NRS) and who were scheduled for laparoscopic donor nephrectomy, robot-assisted laparoscopic donor nephrectomy, or robot-assisted laparoscopic nephrectomy for renal cancer at the University of Rochester Medical Center (URMC) were eligible for enrollment.

Participant flow — Overall Study
MilestoneIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Started108106
Completed108106
Not completed00

Outcome measures

PrimaryTotal Opioid Dose (MME) Used in 24 Hours

Total opiate dose used from the study start (when the first dose of acetaminophen is administered in the pre-anesthesia holding area) to 24 hours post-operatively (in morphine milligram equivalents (MME)).This will include opiates administered intra-operatively.

Time frame:
20 to 24 hours post-operatively
Reported as:
Mean · total morphine milligram equivalents
Total Opioid Dose (MME) Used in 24 Hours
total morphine milligram equivalentsIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Total Opioid Dose (MME) Used in 24 Hours103.61 ± 58.16109.17 ± 57.59
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.3938 · Mean difference (final values): 6.306 · 95% CI -8.242 to 20.854The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryAverage Surgical Pain Intensity

Average surgical pain intensity on a 0-10 numeric rating scale (NRS) administered between 20 and 24 hours post-operatively, with gatekeeping used to control for multiplicity. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

Time frame:
20-24 hours post-operatively
Reported as:
Mean · score on a scale
Average Surgical Pain Intensity
score on a scaleIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Average Surgical Pain Intensity4.87 ± 2.205.00 ± 1.96
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.7051 · Mean difference (final values): 0.107 · 95% CI -0.451 to 0.666The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryAverage Surgical Pain Intensity

Average surgical pain intensity on a 0-10 numeric rating scale (NRS) administered between 20 and 24 hours post-operatively, with gatekeeping used to control for multiplicity. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

Time frame:
1-2 hours post-operatively
Reported as:
Mean · score on a scale
Average Surgical Pain Intensity
score on a scaleIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Average Surgical Pain Intensity4.46 ± 2.344.77 ± 2.41
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.3852 · Mean difference (final values): 0.276 · 95% CI -0.349 to 0.901The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryMean Inspiratory Capacity

The mean inspiratory capacity is presented as a percentage of the subject's baseline (pre-operative) inspiratory capacity, recorded at the time of pain intensity assessments between 1-2 hours postoperatively. Inspiratory capacity is measured using a Voldyne 5000 incentive spirometer (Hudson RCI, Teleflex Medical) and recorded in milliliters to the nearest 250 cc mark on the incentive spirometer. Higher percentages reflect better recovery of inspiratory function.

Time frame:
1-2 hours post-operatively
Reported as:
Mean · percent of baseline inspiratory capacity
Mean Inspiratory Capacity
percent of baseline inspiratory capacityIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Mean Inspiratory Capacity66.60 ± 20.2667.07 ± 20.74
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.8498 · Mean difference (final values): 0.534 · 95% CI -5.02 to 6.088The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryMean Inspiratory Capacity

The mean inspiratory capacity is presented as a percentage of the subject's baseline (pre-operative) inspiratory capacity, recorded at the time of pain intensity assessments between 20-24 hours postoperatively. Inspiratory capacity is measured using a Voldyne 5000 incentive spirometer (Hudson RCI, Teleflex Medical) and recorded in milliliters to the nearest 250 cc mark on the incentive spirometer. Higher percentages reflect better recovery of inspiratory function.

Time frame:
20-24 hours post-operatively
Reported as:
Mean · percent of baseline inspiratory capacity
Mean Inspiratory Capacity
percent of baseline inspiratory capacityIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Mean Inspiratory Capacity64.41 ± 21.8263.35 ± 22.57
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.5839 · Mean difference (final values): -1.650 · 95% CI -7.579 to 4.28The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryDynamic Pain Score During Incentive Spirometer Use

Dynamic pain score on a 0-10 numeric rating scale (NRS) with incentive spirometer use taken during pain intensity assessments at 1-2 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

Time frame:
1-2 hours post-operatively
Reported as:
Mean · score on a scale
Dynamic Pain Score During Incentive Spirometer Use
score on a scaleIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Dynamic Pain Score During Incentive Spirometer Use4.73 ± 2.715.15 ± 2.51
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.2479 · Mean difference (final values): 0.399 · 95% CI -0.280 to 1.078The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryDynamic Pain Score During Incentive Spirometer Use

Dynamic pain score on a 0-10 numeric rating scale (NRS) with incentive spirometer use taken during pain intensity assessments at 20-24 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

Time frame:
20-24 hours post-operatively
Reported as:
Mean · score on a scale
Dynamic Pain Score During Incentive Spirometer Use
score on a scaleIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Dynamic Pain Score During Incentive Spirometer Use4.62 ± 2.565.12 ± 2.25
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.1502 · Mean difference (final values): 0.484 · 95% CI -0.177 to 1.145The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondarySurgical Pain Score During the 20-24 Hour Assessment

Pain intensity on a 0-10 numeric rating scale (NRS) prior to incentive spirometry use was taken during pain intensity assessments at 20-24 hours post-operatively. A larger NRS score means the patient is experiencing more pain, with 0 representing "no pain" and 10 representing "the worst possible pain".

Time frame:
20-24 hours post-operatively
Reported as:
Mean · score on a scale
Surgical Pain Score During the 20-24 Hour Assessment
score on a scaleIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Surgical Pain Score During the 20-24 Hour Assessment3.52 ± 2.253.89 ± 2.14
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.2797 · Mean difference (final values): 0.339 · 95% CI -0.278 to 0.955The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryTime to First Narcotic Use

Time to first postoperative narcotic use, measured in hours (range: 1 to 24).

Time frame:
24 hours post-operatively
Reported as:
Mean · hours
Time to First Narcotic Use
hoursIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Time to First Narcotic Use3.31 ± 5.342.85 ± 4.91
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.6527 · Mean difference (final values): -0.333 · 95% CI -1.792 to 1.125The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryNumber of Participants With Nausea

Number of participants with nausea was assessed based on the administration of anti-emetic medications, with a value of 0 indicating no nausea and 1 indicating the presence of nausea.

Time frame:
24 hours post-operatively
Reported as:
Count of participants · Participants
Number of Participants With Nausea
ParticipantsIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Number of Participants With Nausea5840
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Logistic · p = 0.0499 · Odds ratio (or): 0.465 · 95% CI 0.217 to 1.000Adjusted for age, sex, BMI, type of surgery and TAP block.
SecondaryTime to Discharge From Post-anesthesia Care Unit

Length of time in minutes from PACU(post-anesthesia care unit) arrival to discharge.

Time frame:
24 hours
Reported as:
Mean · Minutes
Time to Discharge From Post-anesthesia Care Unit
MinutesIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Time to Discharge From Post-anesthesia Care Unit174.17 ± 82.99195.48 ± 170.41
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.179 · Mean difference (final values): 24.492 · 95% CI -11.321 to 60.304The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.
SecondaryTime to Hospital Discharge

Number of days to discharge from hospital

Time frame:
30 days
Reported as:
Mean · Days
Time to Hospital Discharge
DaysIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Time to Hospital Discharge2.33 ± 1.302.60 ± 2.27
Statistical analysis
  • IV Acetaminophen and Placebo Pills vs Placebo IV (Normal Saline) + Oral Acetaminophen · Regression, Linear · p = 0.2811 · Mean difference (final values): 0.274 · 95% CI -0.226 to 0.773The estimate reflects the adjusted difference in mean outcome between arms/groups, with the "placebo IV + oral acetaminophen" serving as the reference group.

Adverse events

Collected over Up to 24 hours post-operatively or until hospital discharge. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
IV Acetaminophen and Placebo Pills0/108 (0%)1/108 (0.9%)14/108 (13%)
Placebo IV (Normal Saline) + Oral Acetaminophen0/106 (0%)1/106 (0.9%)16/106 (15.1%)
Most frequent serious events
Most frequent serious events
EventIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Cognitive and attention disordersNervous system disorders0/1081/106
Urinary tract infections and Epididymal and testicular infectionsInfections and infestations0/1081/106
Anemias non-hemolytic and marrow depressionBlood and lymphatic system disorders1/1080/106
Most frequent other events
Showing 10 of 25
Most frequent other events
EventIV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral Acetaminophen
Gastrointestinal symptomsGastrointestinal disorders2/1082/106
Muscle disordersMusculoskeletal and connective tissue disorders0/1082/106
Joint disordersMusculoskeletal and connective tissue disorders2/1082/106
Corneal disordersEye disorders2/1080/106
Respiratory failures and dysfunctionsRespiratory, thoracic and mediastinal disorders2/1080/106
Intraoperative and post-op hemorrhagesVascular disorders2/1080/106
Anemias non-hemolytic and marrow depressionBlood and lymphatic system disorders1/1081/106
Cardiac arrhythmiasCardiac disorders0/1081/106
Body temperature conditionsGeneral disorders0/1081/106
Renal function analysesRenal and urinary disorders0/1081/106

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
<=18 years000
Between 18 and 65 years8076156
>=65 years283058
Age, Continuous
Age, Continuous(Age in years)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
Mean54.0 ± 14.654.4 ± 15.154.2 ± 14.8
Sex: Female, Male
Sex: Female, Male(Participants)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
Female5158109
Male5748105
Race (NIH/OMB)
Race (NIH/OMB)(Participants)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
American Indian or Alaska Native011
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American7411
White94100194
More than one race000
Unknown or Not Reported718
Region of Enrollment
Region of Enrollment(Participants)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
United States108106214
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)IV Acetaminophen and Placebo PillsPlacebo IV (Normal Saline) + Oral AcetaminophenTotal
Hispanic or Latino325
Not Hispanic or Latino9495189
Unknown or Not Reported11920
07

Study locations

1 site
  • University of Rochester Medical Center
    Rochester, New York 14642, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 13, 2023
  • Informed consent form · Jan 13, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03365622
Lead sponsor
University of Rochester
Responsible party
Joseph W Dooley, MD (Associate Professor, University of Rochester) — Principal investigator
First posted
Dec 7, 2017
Start date
Aug 8, 2018
Primary completion
Apr 10, 2024
Completion
Apr 10, 2024
Results posted
Jun 29, 2025
Last update
Jun 29, 2025

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
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