Postoperative PainPhase 3NCT02156154
Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications
A Phase 3 study testing Intravenous Acetaminophen in people with Postoperative Pain, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Some patients have respiratory depression (decreased breaths per minute) after surgery. Acetaminophen, an FDA approved pain medication, may prevent this problem. The purpose of this study is to determine if acetaminophen decreases respiratory depression after surgery. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Intravenous Acetaminophen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 580 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Oct 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent
- 18-85 years old
- above 50 kg
- American Society of Anaesthesiologists Physical Status 1-3
- Scheduled for elective open or laparoscopic abdominal surgery, including colorectal, prostate, and hysterectomy surgeries
- Patients with anticipated hospitalization of two nights
- Expected to require parenteral opioids for at least 48 hours for postoperative pain
- Able to use IV Patient-Controlled Analgesia systems
Who cannot join
- Hepatic disease, e.g. twice the normal levels of liver enzymes
- Kidney disease, e.g. twice the normal level of serum creatinine
- Epidural analgesia or regional blocks (including Transverse abdominis plane block)
- Acetaminophen sensitivity or known allergy
- Female patients who are pregnant or breastfeeding
- Patients taking warfarin
Trial locations and contacts
1 site in 1 country.
About this study
Some patients have respiratory depression (decreased breaths per minute) after surgery. Acetaminophen, an FDA approved pain medication, may prevent this problem. The purpose of this study is to determine if acetaminophen decreases respiratory depression after surgery. The investigators will also evaluate the cost effectiveness of acetaminophen.
Patients having elective major abdominal surgery are being asked to participate in this research study. If eligible, a patient will have their baseline tidal volume (amount of air moved into or out of the lungs) and vital capacity (how much air the lungs are capable of holding) measured using a spirometer (apparatus for measuring the volume of air inspired and expired by the lungs) measured before surgery. Three questionnaires will also need to be completed before surgery.
Read more
The patient will then be randomized, like flipping a coin, to receive either Acetaminophen or placebo (inactive substance) as an infusion throughout surgery and for the first two days thereafter. Neither the patient nor his or her physician will know if the patient is assigned to study drug or placebo. Regardless of study assignment, both groups will receive standard pain management medications and sedation.
After surgery, the patient's blood pressure, activity, posture, respiratory rate, the electrical activity of the heart, oxygen saturation, tidal volume, minute ventilation and respiratory rate will be continuously monitored and recorded for 48 hours using a wireless pulse-oximeter and a respiratory volume monitor.
48 hours after surgery the patient will be asked to complete a patient satisfaction questionnaire, which will allow the patient to rate the satisfaction with the treatment received for pain. The patient will also be asked to complete a questionnaire about recovery.
At discharge, the patient will be given two questionnaires about pain and quality of life.
- Conditions
- Postoperative Pain
- Being tested
- Intravenous Acetaminophen
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous AcetaminophenDrug
| Study group | Role | What they receive |
|---|---|---|
| Intravenous 0.9% sodium chloride | Placebo comparator | 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Receives: Drug: Intravenous Acetaminophen |
| Intravenous Acetaminophen | Experimental | Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Receives: Drug: Intravenous Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Hypoxemia
Hypoxemia is measured as minutes with hypoxemia (Spo2 <90%) per hour of successful Spo2 monitoring. Patients will have nearly continuous pulseoximeter monitoring and recording. Data from the monitor will be downloaded daily for 48 hours postoperatively.
Measured: the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.
Secondary outcomes (9)
Time-weighted Pain Score During Initial 48 Postoperative Hours
Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time. Pain was recorded at roughly 15-minute intervals in the postanesthesia care unit and at 4-hour intervals on surgical wards
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Weighted Pain Score in Post Anesthesia Care Unit
Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time-weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time.
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Fatigue Score on Morning of Postoperative Day 1
Fatigue scores were calculated on a scale of 1 to 10, with 1 being no fatigue and 10 being the worst fatigue imaginable.
Measured: Postoperative day 1
Lowest RASS Score During Initial 48 Postoperative Hours
Sedation was estimated by the RASS score and recorded at 2-hour intervals by ward nurses per clinical routine during the initial 48 postoperative hours. The Richmond Agitation-Sedation Scale (RASS) is scored from -5 to +4, with -5 being unarousable, 0 being alert and calm, and +4 being combative.
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Spent in Sitting or Upright Position
Treatment effect data are reported as ratios of geometric means
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Opioid Consumption - Intravenous Morphine Equivalents
Total opioid consumption over the initial 48 postoperative hours was extracted from patients' medical records and converted to intravenous morphine equivalents
Measured: Initial 48 postoperative hours
Incidence of Postoperative Nausea and Vomiting
Patients were asked about postoperative nausea and vomiting in the postanesthesia care unit, at 4-hour intervals while awake through the remaining initial day of surgery, and on the first and second postoperative mornings.
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Incidence of Low Respiratory Function Event
A low respiratory function event was defined as an episode of less than 40% of predicted minute ventilation for 2 minutes.
Measured: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Total Anesthetic Dose From Induction to Extubation
Total anesthetic dose is measured in minimal alveolar concentration hours.
Measured: Induction to extubation (3 hours on average)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2014 (estimated)
- Study startDec 2014
- Primary completionMar 2019
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 580 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alparslan Turan, The Cleveland Clinic
- Investigators
- Alparslan Turan, M.D., Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02156154
- Sponsor's protocol ID
- 14-241
- Status last verified
- Mar 2021
- First submitted
- 3 Jun 2014
- Last updated
- 20 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Turan A, Essber H, Saasouh W, Hovsepyan K, Makarova N, Ayad S, Cohen B, Ruetzler K, Soliman LM, Maheshwari K, Yang D, Mascha EJ, Ali Sakr Esa W, Kessler H, Delaney CP, Sessler DI; FACTOR Study Group. Effect of Intravenous Acetaminophen on Postoperative Hypoxemia After Abdominal Surgery: The FACTOR Randomized Clinical Trial. JAMA. 2020 Jul 28;324(4):350-358. doi: 10.1001/jama.2020.10009.
PubMed 32721009
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications
- ClinicalTrials.gov ID
- NCT02156154
- Acronym / sponsor ID
- 14-241
- Conditions
- Postoperative Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 580 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Mar 2019 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 5 Jun 2014 (estimated)
- Results
- Posted 20 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some patients have respiratory depression (decreased breaths per minute) after surgery. Acetaminophen, an FDA approved pain medication, may prevent this problem. The purpose of this study is to determine if acetaminophen decreases respiratory depression after surgery. The investigators will also evaluate the cost effectiveness of acetaminophen.
Patients having elective major abdominal surgery are being asked to participate in this research study. If eligible, a patient will have their baseline tidal volume (amount of air moved into or out of the lungs) and vital capacity (how much air the lungs are capable of holding) measured using a spirometer (apparatus for measuring the volume of air inspired and expired by the lungs) measured before surgery. Three questionnaires will also need to be completed before surgery.
The patient will then be randomized, like flipping a coin, to receive either Acetaminophen or placebo (inactive substance) as an infusion throughout surgery and for the first two days thereafter. Neither the patient nor his or her physician will know if the patient is assigned to study drug or placebo. Regardless of study assignment, both groups will receive standard pain management medications and sedation.
After surgery, the patient's blood pressure, activity, posture, respiratory rate, the electrical activity of the heart, oxygen saturation, tidal volume, minute ventilation and respiratory rate will be continuously monitored and recorded for 48 hours using a wireless pulse-oximeter and a respiratory volume monitor.
48 hours after surgery the patient will be asked to complete a patient satisfaction questionnaire, which will allow the patient to rate the satisfaction with the treatment received for pain. The patient will also be asked to complete a questionnaire about recovery.
At discharge, the patient will be given two questionnaires about pain and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous 0.9% sodium chloride | Placebo comparator | Drug: Intravenous Acetaminophen0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. |
| Intravenous Acetaminophen | Experimental | Drug: Intravenous AcetaminophenAcetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written informed consent
- 18-85 years old
- above 50 kg
- American Society of Anaesthesiologists Physical Status 1-3
- Scheduled for elective open or laparoscopic abdominal surgery, including colorectal, prostate, and hysterectomy surgeries
Key exclusion criteria (6 listed)
- Hepatic disease, e.g. twice the normal levels of liver enzymes
- Kidney disease, e.g. twice the normal level of serum creatinine
- Epidural analgesia or regional blocks (including Transverse abdominis plane block)
- Acetaminophen sensitivity or known allergy
- Female patients who are pregnant or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Acetaminophen | Drug | Intravenous 0.9% sodium chloride, Intravenous Acetaminophen |
Primary outcome
Duration of Hypoxemia
Time frame: the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.
Hypoxemia is measured as minutes with hypoxemia (Spo2 <90%) per hour of successful Spo2 monitoring. Patients will have nearly continuous pulseoximeter monitoring and recording. Data from the monitor will be downloaded daily for 48 hours postoperatively.
9 secondary outcomes
Time-weighted Pain Score During Initial 48 Postoperative Hours
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Weighted Pain Score in Post Anesthesia Care Unit
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Fatigue Score on Morning of Postoperative Day 1
Time frame: Postoperative day 1
Lowest RASS Score During Initial 48 Postoperative Hours
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Spent in Sitting or Upright Position
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Opioid Consumption - Intravenous Morphine Equivalents
Time frame: Initial 48 postoperative hours
Incidence of Postoperative Nausea and Vomiting
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Incidence of Low Respiratory Function Event
Time frame: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Total Anesthetic Dose From Induction to Extubation
Time frame: Induction to extubation (3 hours on average)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32721009Turan A, Essber H, Saasouh W, Hovsepyan K, Makarova N, Ayad S, Cohen B, Ruetzler K, Soliman LM, Maheshwari K, Yang D, Mascha EJ, Ali Sakr Esa W, Kessler H, Delaney CP, Sessler DI; FACTOR Study Group. Effect of Intravenous Acetaminophen on Postoperative Hypoxemia After Abdominal Surgery: The FACTOR Randomized Clinical Trial. JAMA. 2020 Jul 28;324(4):350-358. doi: 10.1001/jama.2020.10009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alparslan Turan, M.D. principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous Acetaminophen in people with Postoperative Pain, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Hypoxemia (time frame: the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02156154, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.