Post Operative PainPhase 3NCT02689063
Maxigesic IV Phase 3 Bunionectomy Study
A Phase 3 study testing Maxigesic IV, IV Acetaminophen and IV Ibuprofen in people with Post Operative Pain, run by AFT Pharmaceuticals, Ltd. at 2 sites in United States.
Trial summary
The purpose of the study is to determine the clinical efficacy and safety of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV for the treatment of acute postoperative pain after bunionectomy Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post Operative Pain
- What is being tested?
- Maxigesic IV, IV Acetaminophen and IV Ibuprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 276 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Oct 2016to 15 Sep 2017
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is male or female ≥ 18 and ≤ 65 years of age.
- Is classified by the anesthesiologist as P1 to P2 in the American Society of Anesthesiologists (ASA) Physical Status Classification System.
- Has undergone primary, unilateral, distal, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
- Experiences a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analogue Scale (VAS) during the 9-hour period after discontinuation of the anesthetic block.
- Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2.
- If female and of childbearing potential, is nonlactating and nonpregnant (has negative pregnancy test results at Screening [urine] and on the day of surgery prior to surgery [urine]).
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- If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy, or hysterectomy]) or practicing 1 of the following medically acceptable methods of birth control:
- Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period) before study drug administration.
- Total abstinence from sexual intercourse since the last menses before study drug administration through completion of final study visit.
- Intrauterine device (IUD). Double-barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream).
- Is able to provide written informed consent to participate in the study and able to understand the procedures and study requirements.
- Must voluntarily sign and date an informed consent form (ICF) that is approved by an Institutional Review Board (IRB) before the conduct of any study procedure.
- Is willing and able to comply with study requirements (including diet, alcohol, and smoking restrictions), complete the pain evaluations, remain at the study site for approximately 72 hours, and return for follow-up 7 ± 2 days after surgery.
Who cannot join
- Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen); history of NSAID-induced bronchospasm (subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any other drugs used in the study including anesthetics and antibiotics that may be required on the day of surgery.
- Has experienced any surgical complications or other issues that, in the opinion of the investigator, could compromise the safety of the subject if he or she continues into randomized treatment period or could confound the results of the study.
- Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of screening or evidence of tolerance or physical dependence before dosing with study drug.
- Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease or any other condition that, in the opinion of the investigator, could compromise the subject's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
- Has any ongoing condition, other than a condition associated with the current primary, unilateral, first metatarsal bunionectomy that could generate levels of pain sufficient to confound the results of the study (eg, gout, severe osteoarthritis of the target joint or extremity).
- Has a history or current diagnosis of a significant psychiatric disorder that, in the opinion of the investigator, would affect the subject's ability to comply with the study requirements.
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- Has tested positive either on the urine drug screen or on the alcohol breathalyzer test. Subjects who test positive at Screening only and can produce a prescription for the medication from their physician may be considered for study enrolment at the discretion of the investigator.
- Has a history of a clinically significant (investigator opinion) gastrointestinal (GI) event within 6 months before Screening or has any history of peptic or gastric ulcers or GI bleeding.
- Has a surgical or medical condition of the GI or renal system that might significantly alter the absorption, distribution, or excretion of any drug substance.
- Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for IV Maxigesic®), to be an unsuitable candidate to receive the study drug.
- Is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within 5 years before Screening (excluding treated squamous or basal cell carcinoma of the skin).
- Is currently receiving anticoagulants (eg, heparin or warfarin).
- Has received a course of systemic corticosteroids (either oral or parenteral) within 3 months before Screening (inhaled nasal steroids and regional/limited area application of topical corticosteroids (investigator discretion) are allowed).
- Has received or will require any analgesic medication within 5 half-lives (or, if half-life is unknown, within 48 hours) before surgery.
- Has a history of chronic use (defined as daily use for > 2 weeks) of NSAIDs, opiates, or glucocorticoids (except inhaled nasal steroids and regional/limited topical corticosteroids), for any condition within 6 months before study drug administration. Aspirin at a daily dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the subject has been on a stable dose regimen for ≥ 30 days before Screening and has not experienced any relevant medical problem.
- Has been treated with agents that could affect the analgesic response (such as central alpha agents [clonidine and tizanidine], neuroleptic agents, and other antipsychotic agents) within 2 weeks before dosing with study drug.
- Has a significant renal or hepatic disease, as indicated by clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for any liver function test, including aspartate aminotransferase [AST], alanine aminotransferase [ALT], and lactate dehydrogenase, or creatinine ≥ 1.5 times the ULN).
- Has any clinically significant laboratory finding at Screening that, in the opinion of the investigator, contraindicates study participation.
- Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
- Previously participated in another clinical study of Maxigesic® IV or received any investigational drug or device or investigational therapy within 30 days before Screening.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Optimal Research
Austin, Texas, 78705
Chesapeake Reserach Group
Pasadena, Maryland, 21122
About this study
Official title: Maxigesic IV Bunionectomy Study- A Phase 3, Randomized, Double-Blind, Multiple-Dose, Parallel-Group and Placebo-Controlled Study
The purpose of the study is to determine the clinical efficacy and safety of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV for the treatment of acute postoperative pain after bunionectomy
Read the detailed description
AFT Pharmaceuticals Ltd. has been developing a fixed-dose combination of acetaminophen 1000mg and ibuprofen 300mg/100mL solution for infusion (Maxigesic IV) for the temporary relief of postoperative pain, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration not possible.
A phase 3 efficacy study (AFT-MXIV-07) is proposed to determine the analgesic effects of the fixed dose combination product Maxigesic IV versus its individual components (acetaminophen IV and ibuprofen IV) and placebo in participants with acute post-operative pain after bunionectomy.
The primary efficacy objective is to determine the efficacy of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV as measured by the summed pain intensity difference (SPID) (calculated as a time-weighted average) over 0-48 hours (SPID-48) after time 0.
Other secondary efficacy endpoints are:
VAS Pain intensity difference (PID) at each scheduled assessment time point after Time 0 VAS Pain intensity score at each scheduled assessment time point VAS SPID over 0 to 6 hours (SPID-6), over 0 to 12 hours (SPID-12), and over 0 to 24 hours (SPID-24) after Time 0
Summed pain relief (TOTPAR) (calculated as a time-weighted average) over 0 to 6 hours (TOTPAR-6), over 0 to 12 hours (TOTPAR-12), over 0 to 24 hours (TOTPAR-24) after Time 0, and over 0 to 48 hours (TOTPAR-48) after Time 0
Time to onset of analgesia (measured as time to perceptible pain relief confirmed by meaningful pain relief) using the two-stopwatch method Pain relief score on a 5-point categorical scale at each scheduled time point after Time 0
Peak pain relief
Time to peak pain relief
Time to first perceptible pain relief
Time to meaningful pain relief
Proportion of subjects using rescue medication
Time to first use of rescue medication (duration of analgesia)
Total use of rescue analgesia over 0 to 24 hours and over 0 to 48 hours Patient's global evaluation of study drug
- Conditions
- Post Operative Pain
- Being tested
- Maxigesic IV, IV Acetaminophen, IV Ibuprofen, Placebo IV
- Keywords
- Analgesic
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Maxigesic IVDrug
Also called Maxigesic
IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours
IV AcetaminophenDrug
Also called Acetaminophen
IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours
IV IbuprofenDrug
Also called Ibuprofen
IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours
Placebo IVDrug
Also called Placebo
Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours
| Study group | Role | What they receive |
|---|---|---|
| Maxigesic IV | Experimental | intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours Receives: Drug: Maxigesic IV |
| IV Acetaminophen | Active comparator | IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours Receives: Drug: IV Acetaminophen |
| IV Ibuprofen | Active comparator | IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours Receives: Drug: IV Ibuprofen |
| Placebo IV | Placebo comparator | Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours Receives: Drug: Placebo IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).
A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced.
The extent of pain relief can then be calculated by the Area Under the Curve the PID scores (also referred to as the Sum of Pain Intensity Differences [SPID]). SPID48 scores were adjusted by the time interval from baseline to the final VAS score used in the SPID, using the following formula:
Time-adjusted SPID48 (mm) = SPID (mm*hr) / Time (hr) In the event that a patient required rescue medication, the SPID was calculated up until the first Pre-Rescue VAS pain assessment (inclusive).
Measured: 48 hours after the first dose
Secondary outcomes (13)
VAS Pain Intensity Difference (PID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).
VAS Pain intensity difference (PID) at each scheduled assessment time point after Time 0.
A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced.
Measured: 48 hours after the first dose
VAS Pain Intensity Score-marking on a 100 mm VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm). A High VAS Score Indicates a More Intensive Pain Level Experienced.
VAS Pain intensity score at each scheduled assessment time point VAS pain intensity score-marking on a 100 mm VAS scale with anchors for "no pain" (0 mm) and "worst pain imaginable" (100 mm). A high VAS score indicates a more intensive pain level experienced.
Measured: 48 hours after the first dose
SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose)
Time adjusted SPID-6, SPID-12, SPID-24 were derived in a similar manner to the Time-adjusted SPID-48 (i.e. up until the first Pre-Rescue VAS inclusive). Please see the primary outcome measure descriptions.
Each of these variables were derived from VAS (Visual Analogue Scale) scores recorded prior to the first dose of rescue medication in the first 6 (to calculate SPID6), 12 (to calculate SPID12) or 24 hours (to calculate SPID24) of the study.
VAS pain intensity scores were obtained by marking on a 100 mm VAS scale with anchors for "no pain" (0 mm) and "worst pain imaginable" (100 mm). The VAS was completed at rest.
Measured: 6, 12, 24 hours after the first dose
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48
Total Pain Relief (TOTPAR) is a measure of total Area Under the Curve of Pain Relief scores. In the event that a patient required rescue medication, the TOTPAR endpoints were calculated using Pain Relief Assessments recorded prior to the first dose of rescue (i.e. inclusive of the first pre-rescue Pain Relief score).
Pain relief scores were obtained by marking on a 5-point categorical rating at scheduled time points.
The high score means more pain relief experienced:
0 = No pain relief (the pain is the same, or worse, than the starting pain)
- = A little pain relief (the pain is less than half gone)
- = some pain relief (the pain is about half gone)
- = A lot pain relief (the pain is more than half gone)
- = Complete pain relief (the pain is completely gone) Each of these variables were derived from pain relief scores recorded prior to the first dose of rescue medication in the first 6 (0-48), 12 (0-48), 24 (0-48) or 48 (0-48) hours of the study.
Measured: 6, 12, 24, 48 hours after the first dose
Time to the Onset of Analgesia-Time to Onset of Analgesia (Measured as Time to Perceptible Pain Relief Confirmed by Meaningful Pain Relief) Using the Two-stopwatch Method
Two-stopwatch method
- Start two stopwatches ('Stopwatch A' and 'Stopwatch B') at the same time that the infusion of study drug is initiated. This is Time 0.
- The participant is given 'Stopwatch A' and instructed to "Stop 'Stopwatch A' when you first feel any pain relief whatsoever. This does not mean you feel completely better, although you might, but when you first feel any relief in the pain you have now." (Perceptible Pain Relief)
- When the participant stops the 'Stopwatch A', the participant then was asked "Do you consider the pain relief you experienced meaningful?"
- If the participant answered "No", then the participant was given the "Stopwatch B" and instructed to "Stop 'Stopwatch B' when you feel the pain relief is meaningful to you" (Meaningful Pain Relief)
- If the subject did not experience "perceptible pain relief, they would retain 'Stopwatch A' for the entire 6 hour evaluation period.
Measured: 6 hours
Percentage of Participants With Complete Pain Relief
Pain relief score was assessed on a 5-point categorical scale at each scheduled time point after Time 0:
0 = No pain relief (the pain is the same, or worse, than the starting pain)
- = A little pain relief (the pain is less than half gone)
- = some pain relief (the pain is about half gone)
- = A lot pain relief (the pain is more than half gone)
- = Complete pain relief (the pain is completely gone)
Assessed at scheduled time points:
- 5, 10, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6 hours after the first dose of the study drug
- Immediately before and 2 hours after each subsequent dose (doses 2-8) of the study drug while awake
- At the end of 48 hours of double-blind treatment period
- Immediately before taking each dose of the rescue medication if additional analgesia is required.
- At the time of withdrawal (if applicable)
Measured: 48 hours after the first dose
Percentage of Participants Who Obtained a Peak Pain Relief -Value of 3 ('A Lot of Relief') or 4 ('Complete Relief') Prior to the First Dose of Rescue
Peak Pain Relief was assessed on Pain Relief scores (on a 5 point categorical rating-please see outcome measure description No. 7) recorded up until the first dose of rescue (First Pre-Rescue Pain Relief score inclusive).
The percentage of participants who achieve the peak pain relief was summarized.
Measured: 48 hours after the first dose
Time to Peak Pain Relief
Time to peak pain relief-Peak Pain Relief was assessed on Pain Relief scores recorded up until the first dose of rescue (First Pre-Rescue Pain Relief score inclusive). Time for participants who experienced peak pain relief was summarized.
Note: For the reader to interpret this outcome measure, a very short Time to Peak Pain Relief indicates the absence of analgesic effect for a treatment because peak pain relief was determined prior to the first dose of rescue medication (or 48 hours if no rescue medication was used).
Measured: 48 hrs after the first dose
Percentage of Subjects Using Rescue Medication
The percentage of participants who used at lease one dose of rescue medication was summarized in each treatment group
Measured: 48 hrs after the first dose
Time to the First Dose of Rescue Medication
Time to first use of rescue medication (duration of analgesia)
Measured: 48 hrs
Total Use of Rescue Medication
Total use of rescue analgesia over 0 to 24 hours and over 0 to 48 hours
Measured: 24, 48 hrs after the first dose
The Percentage of Participants Who Evaluated Their Study Drug as " Excellent" on a 5-point Categorical Scale Global Evaluation of Study Drug
At the end of 48 hours study period, participants will be asked to " How do you rate the study medication?" on a 5 point categorical scale:
- Poor
- Fair
- Good
- Very Good
- Excellent The high score means the participants believed that a better treatment for pain relief received.
Measured: 48 hrs after the first dose
Number of Participants With Treatment Emergent Adverse Events (AEs)
Treatment-emergent Adverse events coded to MedDRA v 20.0 Preferred Term and System Organ Class Code were tabulated as the counts and percentages by treatment group.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study start26 Oct 2016
- Primary completion30 Jun 2017
- Study completion15 Sep 2017
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 (2)Papers the sponsor has linked to this study.
- Other trials for Post Operative PainStudies of the same condition, open and under way.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 276 participants (actual)
Sponsor and investigators
- Lead sponsor
- AFT Pharmaceuticals, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen E Daniels, DO, Principal investigator, Optimal Research LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02689063
- Sponsor's protocol ID
- AFT-MXIV-07
- Status last verified
- Feb 2016
- First submitted
- 15 Feb 2016
- Last updated
- 6 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: It is not planned to publish individual participant data.
Publications
Ferguson MC, Schumann R, Gallagher S, McNicol ED. Single-dose intravenous ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev. 2021 Sep 9;9(9):CD013264. doi: 10.1002/14651858.CD013264.pub2.
PubMed 34499349Daniels SE, Playne R, Stanescu I, Zhang J, Gottlieb IJ, Atkinson HC. Efficacy and Safety of an Intravenous Acetaminophen/Ibuprofen Fixed-dose Combination After Bunionectomy: a Randomized, Double-blind, Factorial, Placebo-controlled Trial. Clin Ther. 2019 Oct;41(10):1982-1995.e8. doi: 10.1016/j.clinthera.2019.07.008. Epub 2019 Aug 22.
PubMed 31447129
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maxigesic IV Bunionectomy Study- A Phase 3, Randomized, Double-Blind, Multiple-Dose, Parallel-Group and Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT02689063
- Acronym / sponsor ID
- AFT-MXIV-07
- Conditions
- Post Operative Pain
- Keywords
- Analgesic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 276 participants (actual)
- Lead sponsor
- AFT Pharmaceuticals, Ltd.Industry (pharma, biotech, devices)
- Study start
- 26 Oct 2016 (actual)
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 15 Sep 2017 (actual)
- First posted
- 23 Feb 2016 (estimated)
- Results
- Posted 6 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine the clinical efficacy and safety of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV for the treatment of acute postoperative pain after bunionectomy
Detailed description
AFT Pharmaceuticals Ltd. has been developing a fixed-dose combination of acetaminophen 1000mg and ibuprofen 300mg/100mL solution for infusion (Maxigesic IV) for the temporary relief of postoperative pain, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration not possible.
A phase 3 efficacy study (AFT-MXIV-07) is proposed to determine the analgesic effects of the fixed dose combination product Maxigesic IV versus its individual components (acetaminophen IV and ibuprofen IV) and placebo in participants with acute post-operative pain after bunionectomy.
The primary efficacy objective is to determine the efficacy of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV as measured by the summed pain intensity difference (SPID) (calculated as a time-weighted average) over 0-48 hours (SPID-48) after time 0.
Other secondary efficacy endpoints are:
VAS Pain intensity difference (PID) at each scheduled assessment time point after Time 0 VAS Pain intensity score at each scheduled assessment time point VAS SPID over 0 to 6 hours (SPID-6), over 0 to 12 hours (SPID-12), and over 0 to 24 hours (SPID-24) after Time 0
Summed pain relief (TOTPAR) (calculated as a time-weighted average) over 0 to 6 hours (TOTPAR-6), over 0 to 12 hours (TOTPAR-12), over 0 to 24 hours (TOTPAR-24) after Time 0, and over 0 to 48 hours (TOTPAR-48) after Time 0
Time to onset of analgesia (measured as time to perceptible pain relief confirmed by meaningful pain relief) using the two-stopwatch method Pain relief score on a 5-point categorical scale at each scheduled time point after Time 0
Peak pain relief
Time to peak pain relief
Time to first perceptible pain relief
Time to meaningful pain relief
Proportion of subjects using rescue medication
Time to first use of rescue medication (duration of analgesia)
Total use of rescue analgesia over 0 to 24 hours and over 0 to 48 hours Patient's global evaluation of study drug
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Maxigesic IV | Experimental | Drug: Maxigesic IVintravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours |
| IV Acetaminophen | Active comparator | Drug: IV AcetaminophenIV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours |
| IV Ibuprofen | Active comparator | Drug: IV IbuprofenIV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours |
| Placebo IV | Placebo comparator | Drug: Placebo IVPlacebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Is male or female ≥ 18 and ≤ 65 years of age.
- Is classified by the anesthesiologist as P1 to P2 in the American Society of Anesthesiologists (ASA) Physical Status Classification System.
- Has undergone primary, unilateral, distal, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
- Experiences a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analogue Scale (VAS) during the 9-hour period after discontinuation of the anesthetic block.
- Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2.
Key exclusion criteria (20 listed)
- Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen); history of NSAID-induced bronchospasm (subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any other drugs used in the study including anesthetics and antibiotics that may be required on the day of surgery.
- Has experienced any surgical complications or other issues that, in the opinion of the investigator, could compromise the safety of the subject if he or she continues into randomized treatment period or could confound the results of the study.
- Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of screening or evidence of tolerance or physical dependence before dosing with study drug.
- Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease or any other condition that, in the opinion of the investigator, could compromise the subject's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
- Has any ongoing condition, other than a condition associated with the current primary, unilateral, first metatarsal bunionectomy that could generate levels of pain sufficient to confound the results of the study (eg, gout, severe osteoarthritis of the target joint or extremity).
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 |
|---|---|---|
| Maxigesic IVAlso: MaxigesicIV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours | Drug | Maxigesic IV |
| IV AcetaminophenAlso: AcetaminophenIV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours | Drug | IV Acetaminophen |
| IV IbuprofenAlso: IbuprofenIV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours | Drug | IV Ibuprofen |
| Placebo IVAlso: PlaceboPlacebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours | Drug | Placebo IV |
Primary outcome
Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).
Time frame: 48 hours after the first dose
A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced. The extent of pain relief can then be calculated by the Area Under the Curve the PID scores (also referred to as the Sum of Pain Intensity Differences [SPID]). SPID48 scores were adjusted by the time interval from baseline to the final VAS score used in the SPID, using the following formula: Time-adjusted SPID48 (mm) = SPID (mm*hr) / Time (hr) In the event that a patient required rescue medication, the SPID was calculated up until the first Pre-Rescue VAS pain assessment (inclusive).
13 secondary outcomes
VAS Pain Intensity Difference (PID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).
Time frame: 48 hours after the first dose
VAS Pain Intensity Score-marking on a 100 mm VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm). A High VAS Score Indicates a More Intensive Pain Level Experienced.
Time frame: 48 hours after the first dose
SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose)
Time frame: 6, 12, 24 hours after the first dose
TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48
Time frame: 6, 12, 24, 48 hours after the first dose
Time to the Onset of Analgesia-Time to Onset of Analgesia (Measured as Time to Perceptible Pain Relief Confirmed by Meaningful Pain Relief) Using the Two-stopwatch Method
Time frame: 6 hours
Percentage of Participants With Complete Pain Relief
Time frame: 48 hours after the first dose
Percentage of Participants Who Obtained a Peak Pain Relief -Value of 3 ('A Lot of Relief') or 4 ('Complete Relief') Prior to the First Dose of Rescue
Time frame: 48 hours after the first dose
Time to Peak Pain Relief
Time frame: 48 hrs after the first dose
Percentage of Subjects Using Rescue Medication
Time frame: 48 hrs after the first dose
Time to the First Dose of Rescue Medication
Time frame: 48 hrs
Total Use of Rescue Medication
Time frame: 24, 48 hrs after the first dose
The Percentage of Participants Who Evaluated Their Study Drug as " Excellent" on a 5-point Categorical Scale Global Evaluation of Study Drug
Time frame: 48 hrs after the first dose
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time frame: Day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34499349Ferguson MC, Schumann R, Gallagher S, McNicol ED. Single-dose intravenous ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev. 2021 Sep 9;9(9):CD013264. doi: 10.1002/14651858.CD013264.pub2.
- Derived from this study: PubMed 31447129Daniels SE, Playne R, Stanescu I, Zhang J, Gottlieb IJ, Atkinson HC. Efficacy and Safety of an Intravenous Acetaminophen/Ibuprofen Fixed-dose Combination After Bunionectomy: a Randomized, Double-blind, Factorial, Placebo-controlled Trial. Clin Ther. 2019 Oct;41(10):1982-1995.e8. doi: 10.1016/j.clinthera.2019.07.008. Epub 2019 Aug 22.
- Individual participant dataSharing planned: No. It is not planned to publish individual participant data.
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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.
Stephen E Daniels, DO principal investigator
Optimal Research LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Maxigesic IV, IV Acetaminophen and IV Ibuprofen in people with Post Operative Pain, run by AFT Pharmaceuticals, Ltd. at 2 sites 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 13 inclusion and 20 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 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 6 Jul 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?
Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm). (time frame: 48 hours after the first dose). 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 NCT02689063, which also lists 2 linked publications.
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 6 Jul 2021.