Impacted Wisdom TeethPhase 2CaldolorNCT02133326
Efficacy Study of IV Ibuprofen vs IV Acetaminophen Post Surgical Extraction
A Phase 2 study testing Caldolor and Ofirmev in people with Impacted Wisdom Teeth, run by Tufts University School of Dental Medicine at 2 sites in United States.
Trial summary
This study will compare how effective a single dose of an intravenous (IV) ibuprofen is when compared to single dose of IV acetaminophen in reducing pain. We will administer this study medication thirty minutes prior to removal of wisdom teeth. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Impacted Wisdom Teeth
- What is being tested?
- Caldolor and Ofirmev
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2014to Jan 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients should be at least 18 years old.
- Subjects for whom a decision has been made to extract at least two third molars classified as full or partially bony impacted in the mandible and/or maxilla in an outpatient setting under ambulatory general anesthesia.
- Full bony: The entire tooth is below the level of the alveolar bone.
- Partial bony: A portion of the height of the contour of the tooth is below the level of the alveolar bone.
- Subjects must be physically able to tolerate conventional surgical procedures (ASA I/II)
- Subjects must agree to follow the study protocol.
Who cannot join
- Subjects who are known to be pregnant or think they may be pregnant. (Female patients will be asked to perform a pregnancy test on the day of surgery to confirm they meet study criteria)
- Subjects with known allergy and/or contradiction to ibuprofen and acetaminophen.
- Subjects with history of alcohol or drug abuse (self-reported).
- Subjects who are currently receiving any anti-inflammatory or pain medication or they suffer from a chronic pain condition.
- Subjects that refuse to participate in the follow up protocol including completing pain diaries.
- Actively infected third molars with swelling, trismus, and/or purulent discharge.
- Subjects for whom the lidocaine with epinephrine is contraindicated (e.g., allergy to drug).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tufts University School of Dental Medicine Department of Oral and Maxillofacial Surgery
Boston, Massachusetts, 02111
Tufts University School of Dental Medicine
Boston, Massachusetts, 02111
About this study
Official title: Assessment of Preemptive Analgesic Effect of Caldolor® vs. Ofirmev® on Third Molar Surgery: A Prospective, Randomized, Double-blinded Clinical Trial
This study will compare how effective a single dose of an intravenous (IV) ibuprofen is when compared to single dose of IV acetaminophen in reducing pain. We will administer this study medication thirty minutes prior to removal of wisdom teeth. We want to see if administering these drugs prior to surgery may reduce post-operative pain.
Administration of nonsteroidal anti-inflammatory drug before the onset of inflammation during surgery will reduce postoperative pain following third molar extraction when compared to the acetaminophen group. Subjects receiving nonsteroidal anti-inflammatory drug will consume less opioid medications compared to those receiving preemptive acetaminophen.
Read the detailed description
The surgical removal of third molars is a common surgical procedure performed in dentistry. Surgery to extract an impacted third molar can be due to various reasons such as infection, caries, pain, cyst or tumor formation, or to facilitate orthodontic treatment. Both clinicians and patients are concerned with the postoperative pain following surgery.
Rationale for model selection The oral surgery model is well-suited for the measurement of acute pain.The model has been shown to be sensitive to the effects of analgesic drugs and is useful for examining peripheral biochemical measures of drugs in vivo.This model is recommended by the US Food and Drug Administration because patients are usually healthy without complicating medical conditions and most patients have pain for a short, predictable period after surgery.
Rationale for drug selection Pain from the surgical incision and tissue manipulation associated with the surgical procedure is instigated immediately. This gives way to inflammatory pain that follows inflammatory cell recruitment to the injured area within the course of several hours. Inflammatory pain generally continues for several days, depending on the nature of the surgical procedure. As a consequence of tissue damage and release of neurogenic inflammatory mediators, there is activation of specific receptors and pathways that can contribute to central sensitization and development of hyperalgesia and persistent pain. While various pharmacological strategies, including the use of opioids, provide adequate attenuation of pain, their use is associated with undesirable side effects, drug interactions, pharmacokinetic variability, and often inadequate dosing, all of which can lead to ineffective analgesia and prolonged suffering. Opioids do not interrupt the inflammatory component of pain.
The study drug Caldolor® is an intravenous formulation of ibuprofen which was approved by the FDA in June 2009. Caldolor® is the first injectable product available in the United States for the treatment of pain and fever. This is the first study in dentistry evaluating the use of Caldolor® as a preemptive analgesia. Southworth et al and colleagues randomized 406 patients undergoing elective single-site orthopedic or abdominal surgery to 400 mg intravenous (IV) Caldolor, 800 mg IV Caldolor, or placebo. The results showed that patients in the 800 mg group had a 25.6% lower median morphine use (P = .026) over the first 24 hours of treatment than the placebo group. Patients in the 400 mg group did not have a lower use of morphine, but both the 400 and 800 mg groups reported less pain at rest and with movement than with placebo.
The comparator group Ofirmev® is intravenous acetaminophen and was recently approved by the FDA for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, and the reduction of fever. In a study conducted for total abdominal hysterectomy, preemptive IV paracetamol (acetaminophen) 1 g provided good quality postoperative analgesia, with decreased consumption of morphine and minimal side effects. Studies have showed that the use of 1 g of paracetamol as a single intravenous preemptive dose in abdominal surgery with perioperative epidural analgesia did not reduce the analgesic consumption and the intensity of pain in the postoperative period.
Use of Pain Scale VAS Pain Scale Score: The primary end point is the clinical report of pain. Pain intensity will be assessed using a 100 mm VAS with anchors of "no pain" and "worst pain imaginable" and a 4-point category scale ("none", "mild", "moderate", and "severe") once pre-operatively and over the post-operative observation period at 30-minute intervals during the post- surgical time. The category scale is included for purposes of obtaining a patient-reported assignment of moderate pain (definition of clinically significant pain), and for computing the cut-offs for pain sensitivity.
- Conditions
- Impacted Wisdom Teeth
- Being tested
- Caldolor, Ofirmev
- Keywords
- Analgesia, Third Molar Extraction, Ibuprofen, Acetaminophen, Pain Medicine, Nonsteroidal, Anti-inflammatory
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaldolorDrug
Also called IV Ibuprofen
Subject will be given Caldolor by IV prior to surgery.
OfirmevDrug
Also called Acetaminophen
Subject will be given Ofirmev prior to surgery.
| Study group | Role | What they receive |
|---|---|---|
| Caldolor | Experimental | 800 mg of Caldolor® will be infused at the rate of 5-7 minutes as per the manufacturer's guidelines or Receives: Drug: Caldolor |
| Ofirmev | Experimental | 1000 mg of Ofirmev® will be infused at the rate of 15 minutes as per the manufacturer's guidelines. Receives: Drug: Ofirmev |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of IV ibuprofen for post-op pain.
To determine the efficacy of a single dose of intravenous ibuprofen administered over 5-10 minutes for the preemptive treatment of postoperative pain following third molar extraction.The post operative pain intensity will be measured using (Visual Analog Scale, VAS). A total of 9 pain ratings will be obtained:
- Prior to surgery
- Immediately after the subject wakes from anesthesia
- First onset of pain (typically 45 minutes-1.5 hours after procedure)
- 4 hours post-operative
- 24 hours post-operative
- 48 hours post-operative
- 72 hours post-operative
- Day 7 post-operative
Measured: 7 days post-operative
Secondary outcomes (1)
Pain medication consumption
To determine any difference in the percentage of pain medications consumed post operatively in both the groups.
Measured: Post 3rd molar extraction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2014 (estimated)
- Study startMar 2014
- Primary completionJan 2017 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Impacted Wisdom TeethStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University School of Dental Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Archana Viswanath, BDS,MS, Principal investigator, Tufts University School of Dental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02133326
- Sponsor's protocol ID
- Caldolor vs. Orfimev Clinical
- Acronym
- Caldolor
- Status last verified
- Oct 2016
- First submitted
- 17 Sep 2013
- Last updated
- 20 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hargreaves KM, Troullos ES, Dionne RA. Pharmacologic rationale for the treatment of acute pain. Dent Clin North Am. 1987 Oct;31(4):675-94.
PubMed 3319716Dionne RA, Khan AA, Gordon SM. Analgesia and COX-2 inhibition. Clin Exp Rheumatol. 2001 Nov-Dec;19(6 Suppl 25):S63-70.
PubMed 11695255Gordon SM, Brahim JS, Rowan J, Kent A, Dionne RA. Peripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia: replicate clinical trials in a tissue injury model. Clin Pharmacol Ther. 2002 Aug;72(2):175-83. doi: 10.1067/mcp.2002.126501.
PubMed 12189364Ridgway D. Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy. Clin J Pain. 2004 May-Jun;20(3):123-32. doi: 10.1097/00002508-200405000-00001.
PubMed 15100587Southworth S, Peters J, Rock A, Pavliv L. A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain. Clin Ther. 2009 Sep;31(9):1922-35. doi: 10.1016/j.clinthera.2009.08.026.
PubMed 19843482Arici S, Gurbet A, Turker G, Yavascaoglu B, Sahin S. Preemptive analgesic effects of intravenous paracetamol in total abdominal hysterectomy. Agri. 2009 Apr;21(2):54-61.
PubMed 19562533Borisov, D Preemptive analgesia with paracetamol in postoperative analgesia for abdominal surgery: 14AP5-2 European Journal of Anaesthesiology: June 2007 - Volume 24 - Issue - p 179
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Preemptive Analgesic Effect of Caldolor® vs. Ofirmev® on Third Molar Surgery: A Prospective, Randomized, Double-blinded Clinical Trial
- ClinicalTrials.gov ID
- NCT02133326
- Acronym / sponsor ID
- Caldolor / Caldolor vs. Orfimev Clinical
- Conditions
- Impacted Wisdom Teeth
- Keywords
- Analgesia, Third Molar Extraction, Ibuprofen, Acetaminophen, Pain Medicine, Nonsteroidal, Anti-inflammatory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Tufts University School of Dental MedicineUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 8 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare how effective a single dose of an intravenous (IV) ibuprofen is when compared to single dose of IV acetaminophen in reducing pain. We will administer this study medication thirty minutes prior to removal of wisdom teeth. We want to see if administering these drugs prior to surgery may reduce post-operative pain.
Administration of nonsteroidal anti-inflammatory drug before the onset of inflammation during surgery will reduce postoperative pain following third molar extraction when compared to the acetaminophen group. Subjects receiving nonsteroidal anti-inflammatory drug will consume less opioid medications compared to those receiving preemptive acetaminophen.
Detailed description
The surgical removal of third molars is a common surgical procedure performed in dentistry. Surgery to extract an impacted third molar can be due to various reasons such as infection, caries, pain, cyst or tumor formation, or to facilitate orthodontic treatment. Both clinicians and patients are concerned with the postoperative pain following surgery.
Rationale for model selection The oral surgery model is well-suited for the measurement of acute pain.The model has been shown to be sensitive to the effects of analgesic drugs and is useful for examining peripheral biochemical measures of drugs in vivo.This model is recommended by the US Food and Drug Administration because patients are usually healthy without complicating medical conditions and most patients have pain for a short, predictable period after surgery.
Rationale for drug selection Pain from the surgical incision and tissue manipulation associated with the surgical procedure is instigated immediately. This gives way to inflammatory pain that follows inflammatory cell recruitment to the injured area within the course of several hours. Inflammatory pain generally continues for several days, depending on the nature of the surgical procedure. As a consequence of tissue damage and release of neurogenic inflammatory mediators, there is activation of specific receptors and pathways that can contribute to central sensitization and development of hyperalgesia and persistent pain. While various pharmacological strategies, including the use of opioids, provide adequate attenuation of pain, their use is associated with undesirable side effects, drug interactions, pharmacokinetic variability, and often inadequate dosing, all of which can lead to ineffective analgesia and prolonged suffering. Opioids do not interrupt the inflammatory component of pain.
The study drug Caldolor® is an intravenous formulation of ibuprofen which was approved by the FDA in June 2009. Caldolor® is the first injectable product available in the United States for the treatment of pain and fever. This is the first study in dentistry evaluating the use of Caldolor® as a preemptive analgesia. Southworth et al and colleagues randomized 406 patients undergoing elective single-site orthopedic or abdominal surgery to 400 mg intravenous (IV) Caldolor, 800 mg IV Caldolor, or placebo. The results showed that patients in the 800 mg group had a 25.6% lower median morphine use (P = .026) over the first 24 hours of treatment than the placebo group. Patients in the 400 mg group did not have a lower use of morphine, but both the 400 and 800 mg groups reported less pain at rest and with movement than with placebo.
The comparator group Ofirmev® is intravenous acetaminophen and was recently approved by the FDA for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, and the reduction of fever. In a study conducted for total abdominal hysterectomy, preemptive IV paracetamol (acetaminophen) 1 g provided good quality postoperative analgesia, with decreased consumption of morphine and minimal side effects. Studies have showed that the use of 1 g of paracetamol as a single intravenous preemptive dose in abdominal surgery with perioperative epidural analgesia did not reduce the analgesic consumption and the intensity of pain in the postoperative period.
Use of Pain Scale VAS Pain Scale Score: The primary end point is the clinical report of pain. Pain intensity will be assessed using a 100 mm VAS with anchors of "no pain" and "worst pain imaginable" and a 4-point category scale ("none", "mild", "moderate", and "severe") once pre-operatively and over the post-operative observation period at 30-minute intervals during the post- surgical time. The category scale is included for purposes of obtaining a patient-reported assignment of moderate pain (definition of clinically significant pain), and for computing the cut-offs for pain sensitivity.
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 |
|---|---|---|
| Caldolor | Experimental | Drug: Caldolor800 mg of Caldolor® will be infused at the rate of 5-7 minutes as per the manufacturer's guidelines or |
| Ofirmev | Experimental | Drug: Ofirmev1000 mg of Ofirmev® will be infused at the rate of 15 minutes as per the manufacturer's guidelines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients should be at least 18 years old.
- Subjects for whom a decision has been made to extract at least two third molars classified as full or partially bony impacted in the mandible and/or maxilla in an outpatient setting under ambulatory general anesthesia.
- Subjects must be physically able to tolerate conventional surgical procedures (ASA I/II)
- Subjects must agree to follow the study protocol.
Key exclusion criteria (7 listed)
- Subjects who are known to be pregnant or think they may be pregnant. (Female patients will be asked to perform a pregnancy test on the day of surgery to confirm they meet study criteria)
- Subjects with known allergy and/or contradiction to ibuprofen and acetaminophen.
- Subjects with history of alcohol or drug abuse (self-reported).
- Subjects who are currently receiving any anti-inflammatory or pain medication or they suffer from a chronic pain condition.
- Subjects that refuse to participate in the follow up protocol including completing pain diaries.
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 |
|---|---|---|
| CaldolorAlso: IV IbuprofenSubject will be given Caldolor by IV prior to surgery. | Drug | Caldolor |
| OfirmevAlso: AcetaminophenSubject will be given Ofirmev prior to surgery. | Drug | Ofirmev |
Primary outcome
Efficacy of IV ibuprofen for post-op pain.
Time frame: 7 days post-operative
To determine the efficacy of a single dose of intravenous ibuprofen administered over 5-10 minutes for the preemptive treatment of postoperative pain following third molar extraction.The post operative pain intensity will be measured using (Visual Analog Scale, VAS). A total of 9 pain ratings will be obtained: 1. Prior to surgery 2. Immediately after the subject wakes from anesthesia 3. First onset of pain (typically 45 minutes-1.5 hours after procedure) 4. 4 hours post-operative 5. 24 hours post-operative 6. 48 hours post-operative 7. 72 hours post-operative 8. Day 7 post-operative
1 secondary outcome
Pain medication consumption
Time frame: Post 3rd molar extraction
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2017.
- Background: PubMed 3319716Hargreaves KM, Troullos ES, Dionne RA. Pharmacologic rationale for the treatment of acute pain. Dent Clin North Am. 1987 Oct;31(4):675-94.
- Background: PubMed 11695255Dionne RA, Khan AA, Gordon SM. Analgesia and COX-2 inhibition. Clin Exp Rheumatol. 2001 Nov-Dec;19(6 Suppl 25):S63-70.
- Background: PubMed 12189364Gordon SM, Brahim JS, Rowan J, Kent A, Dionne RA. Peripheral prostanoid levels and nonsteroidal anti-inflammatory drug analgesia: replicate clinical trials in a tissue injury model. Clin Pharmacol Ther. 2002 Aug;72(2):175-83. doi: 10.1067/mcp.2002.126501.
- Background: PubMed 15100587Ridgway D. Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy. Clin J Pain. 2004 May-Jun;20(3):123-32. doi: 10.1097/00002508-200405000-00001.
- Background: PubMed 19843482Southworth S, Peters J, Rock A, Pavliv L. A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain. Clin Ther. 2009 Sep;31(9):1922-35. doi: 10.1016/j.clinthera.2009.08.026.
- Background: PubMed 19562533Arici S, Gurbet A, Turker G, Yavascaoglu B, Sahin S. Preemptive analgesic effects of intravenous paracetamol in total abdominal hysterectomy. Agri. 2009 Apr;21(2):54-61.
- BackgroundBorisov, D Preemptive analgesia with paracetamol in postoperative analgesia for abdominal surgery: 14AP5-2 European Journal of Anaesthesiology: June 2007 - Volume 24 - Issue - p 179
- Individual participant dataSharing planned: No
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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.
Archana Viswanath, BDS,MS principal investigator
Tufts University School of Dental Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Caldolor and Ofirmev in people with Impacted Wisdom Teeth, run by Tufts University School of Dental Medicine 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 6 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 20 Jan 2017. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Efficacy of IV ibuprofen for post-op pain. (time frame: 7 days post-operative). 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 NCT02133326, which also lists 7 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 20 Jan 2017.