A Pilot Trial to Determine the Effective Dose of N-acetylcysteine for Opioid Reduction in Patients Undergoing Spine Surgery.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Opioid Consumption 12 Hours Post Operative
Study Overview
Brief Summary
Determine the optimal dose of IV N-acetylcysteine (NAC) to produce opioid reduction following spine surgery and estimate the difference in opioid consumption between placebo and the selected optimal dose.
Detailed Description
First 20 subjects: 5 participants will be randomized to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose.
If the dose response curve is adequate and the optimal dose identified, 15 additional participants will be randomized to placebo and 15 to the optimal dose to estimate the difference in opioid consumption between participants on placebo vs. the optimal dose. (Total of 50 subjects with 20 from dose response curve and 30 to estimate the difference in opioid consumption.)
If the dose response curve is not adequate after the initial 20 subjects 5 per each dose group, then an additional 5 participants will be randomized and to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose. Once the optimal dose is identified with these initial 40 patients, 10 additional participants will be randomized to placebo and 10 to the optimal dose to estimate the difference in opioid consumption between participants on placebo vs. the optimal dose. (60 patients total with 40 to create the dose response curve and 20 more to estimate the difference in opioid consumption.)
A sample size of 20 subjects per group (placebo and optimal dose) allows us to estimate a 95% confidence interval for the mean difference in opioid consumption with a width of + 0.64 standard deviations from the mean. 70 subjects may be enrolled to account for withdrawal but the study will be completed once 50 or 60 subjects (based on the number of subjects required to create the dose response curve) have completed the protocol.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Undergoing elective spine surgery involving 4 levels or less of the thoracic, lumbar, or sacral spine.
- •18 years of age and older.
Exclusion Criteria
- •Less than 40kg in weight.
- •Unable to provide written, informed consent.
- •History of an adverse or anaphylactoid reaction to acetylcysteine.
- •Active asthma, wheezing, or using inhaled bronchodilators.
- •Pregnant Women
- •Known blood clotting deficiency
Arms & Interventions
Dose Response Curve Placebo
5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose.
Intervention: Dose Response Curve Placebo (Drug)
Dose Response Curve N-acetylcysteine 50 mg/kg
5 participants will be randomized to the N-acetylcysteine 50 mg/kg group to estimate the dose response curve and to identify the optimal dose.
Intervention: Dose Response Curve N-acetylcysteine 50 mg/kg (Drug)
Dose Response Curve N-acetylcysteine 100 mg/kg
5 participants will be randomized to the N-acetylcysteine 100 mg/kg group to estimate the dose response curve and to identify the optimal dose.
Intervention: Dose Response Curve N-acetylcysteine 100 mg/kg (Drug)
Dose Response Curve N-acetylcysteine 150 mg/kg
5 participants will be randomized to the N-acetylcysteine 150 mg/kg group to estimate the dose response curve and to identify the optimal dose.
Intervention: Dose Response Curve N-acetylcysteine 150 mg/kg (Drug)
Opioid Reduction with Optimal N-acetylcysteine Dose
Once the optimal N-acetylcysteine dose is identified, 15 additional participants will be randomized to the optimal dose to estimate the difference in opioid consumption between patients on placebo vs. the optimal dose. Primary and secondary outcomes will only be evaluated for the placebo group and optimal NAC group.
Intervention: Opioid Reduction with Optimal N-acetylcysteine Dose (Drug)
Placebo
15 Participants will be randomized to placebo to estimate the difference in opioid consumption between patients on placebo vs. the optimal dose. Primary and secondary outcomes will only be evaluated for the placebo group and optimal NAC group.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Opioid Consumption 12 Hours Post Operative
Time Frame: 12 hours
Post operative opioid consumption in the 12 hours that occur post-operatively.
Secondary Outcomes
- Opioid Consumption Every 6 Hours Post Operative(6-48 hours)
Investigators
Sylvia Wilson
Professor
Medical University of South Carolina