A Pilot Trial to Determine the Effective N-acetylcysteine Dose for Opioid Reduction for Spine Surgery.

Phase 1

Completed

Conditions: Surgery

Interventions: Drug: Dose Response Curve N-acetylcysteine 100 mg/kg
Drug: Dose Response Curve N-acetylcysteine 50 mg/kg
Drug: Dose Response Curve Placebo
Drug: Opioid Reduction with Optimal N-acetylcysteine Dose
Drug: Dose Response Curve N-acetylcysteine 150 mg/kg
Drug: Placebo

Registration Number: NCT04562597

Lead Sponsor: Medical University of South Carolina

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Response Curve N-acetylcysteine 100 mg/kg	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.
Dose Response Curve N-acetylcysteine 50 mg/kg	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.
Dose Response Curve Placebo	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.
Opioid Reduction with Optimal N-acetylcysteine Dose	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.
Dose Response Curve N-acetylcysteine 150 mg/kg	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.
Placebo	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.

Primary Outcome Measures

Name	Time	Method
Opioid Consumption 12 Hours Post Operative	12 hours	Post operative opioid consumption in the 12 hours that occur post-operatively.

Secondary Outcome Measures

Name	Time	Method
Opioid Consumption Every 6 Hours Post Operative	6-48 hours	Post operative opioid consumption ry 6 hours post operative. Data are reported as mean (95% CI) or mean difference (95% CI) estimated from a linear mixed model of opioid consumption over time including main effects for treatment group, postoperative time, and the interaction between treatment group and postoperative time and a random subject effect.