Rofecoxib to Prevent Pain After Third Molar (Wisdom Tooth) Extraction
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain
Intervention: Rofecoxib (Drug)
Phase: Phase 2
Sponsored by: National Institute of Dental and Craniofacial Research (NIDCR)
This study will evaluate the ability of a new non-steroidal anti-inflammatory drug (NSAID)
called rofecoxib to prevent pain following third molar (wisdom tooth) extraction. The Food
and Drug Administration approved rofecoxib in 1999 to treat the symptoms of arthritis,
menstrual cramps, and pain.
Healthy normal volunteers between 16 and 35 years of age in general good health who require
third molar (wisdom tooth) extraction may be eligible for this study. Candidates will be
screened with a medical history and oral examination, including dental x-rays as needed to
confirm the need for third molar removal.
Participants will have all four wisdom teeth extracted, and a biopsy (removal of a small
piece of tissue) will be taken from the inside of the cheek around the area behind the lower
wisdom tooth. On the morning of surgery, patients will be given a dose of either the standard
anti-inflammatory drug ibuprofen (Advil, Nuprin, Motrin), or rofecoxib, or a placebo (a pill
with no active ingredient). Before surgery, they will be given a local anesthetic (lidocaine)
in the mouth and a sedative (midazolam) through an arm vein.
After the surgery, patients will remain in the clinic for up to 4 hours to monitor pain and
the effects of the drug. Patients will complete pain questionnaires. Patients whose pain is
unrelieved an hour after surgery may request and receive morphine intravenously (through a
vein). After 4 hours, patients will be discharged with additional pain medicines (Tylenol
with codeine and the study drug) and instructions for their use. They will also be given a
pain diary to record pain ratings and medications taken at home. A clinic staff member will
telephone patients at home the morning after surgery to ensure they are rating their pain
intensity at the proper time and are taking their medications as instructed.
Patients will return to the clinic 48 hours after surgery with the pain diary and pain
relievers. At this visit, another biopsy will be taken under local anesthetic.
Official title: Pre-Emptive Analgesic Effects of a Selective COX-2 Inhibitor (Rofecoxib) in the Oral Surgery Model
Study design: Treatment, Safety/Efficacy Study
Pain and inflammation are predictable sequelae following tissue injury, such as surgery.
Conventional treatment for intraoperative and postoperative control of pain includes local
anesthetic administered preoperatively and analgesics administered postoperatively.
Disadvantages of these approaches include pain during the interval when the effect of local
anesthesia dissipates and the postoperatively administered analgesic takes effect and adverse
effects of opioid-containing analgesics in ambulatory patients. Research over the past two
decades has demonstrated that administering nonsteroidal anti-inflammatory drugs (NSAIDs)
preoperatively significantly reduces the intensity and the duration of postoperative pain up
to eight hours (Dionne et al., 1978 and Jackson et al., 1989). Parallel clinical
investigations suggest that the pre-emptive treatment with a long-acting local anesthetic or
an NMDA-antagonist reduces pain at 24 to 72 hours post-surgery (Gordon et al., 1997; Yamamoto
et al., 1993; Gordon et al., 1999). This proposed clinical trial will use the oral surgery
model to assess the therapeutic efficacy of pre-emptive and preventive treatment with a
potent selective COX-2 inhibitor, rofecoxib (Vioxx® (Registered Trademark)), given prior to
and following third molar extractions to reduce postoperative pain at 24 and 48 hours
This study is a double-blind, randomized control trial with parallel groups using placebo,
ibuprofen, or rofecoxib. Rofecoxib 50 mg will be administered PO 90 minutes before surgery
in the Clinical Center at NIH and another 50 mg will be self-administered 24 hours later by
the subjects at their homes. This regimen is predicted to suppress the onset and intensity
of post-operative dental pain to a greater extent than placebo or a non-selective COX-1/COX-2
inhibitor (ibuprofen). The analgesic effect of the drugs will be estimated by hourly
observations over the first four hours after surgery using two different measures of pain
intensity, the category scale and a visual analog scale (VAS). It is hypothesized that the
pre-emptive administration of a selective COX-2 inhibitor, rofecoxib will inhibit the
development of central and peripheral sensitization following tissue injury which manifests
as hyperalgesia at later time points.
Minimum age: N/A.
Maximum age: N/A.
Male or female volunteers referred for third molar extraction willing to undergo 3 visits:
1 screening visit, 1 surgical appointment, and 1 follow-up research-related appointment.
Between the ages of 16 to 35 years (based upon eruption patterns and age-related
complications associated with surgical extraction of third molars)
In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy
subjects based upon criteria for safe administration of out-patient conscious sedation)
Willing to undergo observation period for four hours post-operatively
Willing to complete a 100 mm visual analog scale and a category scale every hour for the
first 4 post-operative hours, and again at 24 and 48 hours
Willing to have a preoperative biopsy on the day of surgery and a postoperative biopsy at
Willing to return 48 hours to return completed pain diaries and for the postoperative
Sum total of the assessment of surgical difficulty ratings (Screening visit) must be
between 8 to 14 in order to evaluate subjects experiencing similar pain levels.
Allergy to aspirin or NSAIDS
Pregnant or lactating females
History of peptic ulcers and GI bleeding
Chronic use of medications confounding the assessment of the inflammatory response or
analgesia ( antihistamines, NSAIDS, steroids, antidepressants, sulfa drugs)
Presence of a clinical signs suggestive of infection or inflammation
Unusual surgical difficulty
Surgical difficulty assessment rating less than 8 or greater than 14
Locations and Contacts
National Institute of Dental And Craniofacial Research (NIDCR), Bethesda, Maryland 20892, United States
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528.
Dionne RA, Campbell RA, Cooper SA, Hall DL, Buckingham B. Suppression of postoperative pain by preoperative administration of ibuprofen in comparison to placebo, acetaminophen, and acetaminophen plus codeine. J Clin Pharmacol. 1983 Jan;23(1):37-43.
Bannwarth B, Netter P, Pourel J, Royer RJ, Gaucher A. Clinical pharmacokinetics of nonsteroidal anti-inflammatory drugs in the cerebrospinal fluid. Biomed Pharmacother. 1989;43(2):121-6. Review.
Starting date: November 2001
Ending date: November 2003
Last updated: March 3, 2008