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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Trial to Determine the Effective Dose of N-acetylcysteine for Opioid Reduction in Patients Undergoing Spine Surgery.

Conditions
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Surgery

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: PHASE I. First 20 subjects (4 arms): We will initially randomize 5 patients to each dose group (placebo, 50, 100, and 150 mg/kg) to estimate the dose response curve and to identify the optimal dose. After enrollment of the first 20 patients, the study will undergo review by the study team and statistician. PHASE II: (2 arms) 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 patients on placebo vs. the optimal dose. Primary and secondary outcomes will be evaluated only for the placebo and optimal NAC groups.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dose Response Curve Placebo<br>5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose. | Drug: Dose Response Curve Placebo<br>* 5 participants will be randomized to the placebo group to estimate the dose response curve and to identify the optimal dose.<br>|
| Active Comparator: Dose Response Curve N-acetylcysteine 50 mg/kg<br>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. | Drug: Dose Response Curve N-acetylcysteine 50 mg/kg<br>* 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.<br>|
| Active Comparator: Dose Response Curve N-acetylcysteine 100 mg/kg<br>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. | Drug: Dose Response Curve N-acetylcysteine 100 mg/kg<br>* 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.<br>|
| Active Comparator: Dose Response Curve N-acetylcysteine 150 mg/kg<br>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. | Drug: Dose Response Curve N-acetylcysteine 150 mg/kg<br>* 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.<br>|
| Active Comparator: Opioid Reduction with Optimal N-acetylcysteine Dose<br>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. | Drug: Opioid Reduction with Optimal N-acetylcysteine Dose<br>* Once the optimal N-acetylcysteinedose is identified, 15 participants will be randomized to the optimal dose (50,100, or 150 mg/kg) to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 15 Participants will be randomized to placebo to estimate the difference in opioid consumption between patients administered optimal N-acetylcysteine dose or placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Consumption 12 Hours Post Operative | Post operative opioid consumption in the 12 hours that occur post-operatively. | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Consumption Every 6 Hours Post Operative | 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. | 6-48 hours |