A Phase II/III Study of Continuous Local Anesthetic Infusion in Median Sternotomy Following Cardiac Surgery

Study Overview
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Brief Summary
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Cardiac surgery is associated with pain in the post-operative period. We plan to conduct a study of local anesthetic, ropivacaine, infusion into the sternal wound in adult patients undergoing cardiac surgery to see if it will be safe and result in improved pain control and reduced time to extubation, duration of ICU and hospital stay.

Detailed Description
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Background: Cardiac surgery is associated with pain in the post-operative period. Recently the ability to infuse local anesthetic drugs into the area of the sternal wound has become available. The studies that have been done thus far have shown efficacy in controlling pain but have been too small to show clinically significant patient outcome differences. Specific Aim: We plan to conduct a phase II/III study of local anesthetic infusion into the sternal wound in adult patients undergoing cardiac surgery. In the Phase II study, 40 patients will be enrolled in a prospective observational open label, dose escalation study of safety and efficacy of local anesthetic infusion into the sternal wound. Outcome measures for efficacy will be visual analog pain (VAP) scores and opioid consumption. Outcome measures for safety will be plasma ropivacaine concentrations and adverse events. The dose determined in the phase II study will be used in the Phase III study. In this study, 200 patients will be enrolled in a double blind prospective, randomized, double blind; placebo controlled trial of local anesthetic infusion into the sternal wound. Outcome measures for efficacy will be visual analog pain (VAP) scores, opioid consumption, time to extubation, pulmonary function tests, duration of ICU and hospital stay, all cause morbidity and mortality. Outcome measure for safety will be adverse events. Hypothesis: Local anesthetic infusion into the sternal wound will be safe and result in improved pain control and reduced time to extubation, duration of ICU and hospital stay. Significance: This will be the first large randomized controlled clinical trial assessing outcomes with the use of local anesthetic infusion into the sternal wound in patients undergoing open-heart surgery.

Official Title
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A Phase II/III Study of Continuous Local Anesthetic Infusion in Median Sternotomy Following Cardiac Surgery

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Drug: Ropivacaine
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be greater than 18 years of age Be undergoing a cardiac surgical procedure via median sternotomy (i.e., exclude the occasional thoracotomy, since much greater pain with that surgical approach post-operatively) Exclusion Criteria: Are unable to grant informed consent or comply with study procedure Are undergoing emergency open heart-surgery Allergic to any of the excipients in ropivacaine, propofol, and fentanyl Age < 18 years of age (children have dosing and toxicity concerns) Are pregnant (pregnancy changes pain thresholds) Taking preoperative opioids. (Opioid tolerant patients will require significantly more post-operative opioid use.) Cirrhosis or hepatic failure (may have accumulation of local anesthetic in plasma due to decreased metabolism) Patient receiving lidocaine infusion prior to surgery. (An extremely rare event) Patients having a planned circulatory arrest for their surgical procedure (increased duration of intubation possible)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Ropivicaine infusion into the sternal wound | Drug: Ropivacaine<br>* 0.3% ropivacaine infusion at 4 ml/hr for 64 hours.<br>|
| Placebo Comparator: 2<br>Normal saline infusion into the sternal wound | Drug: Normal saline<br>* Normal saline infusion at 4 ml/hour for 64 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analog pain |  | 64 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| drug toxicity |  | 64 hours | 
| infection |  | 64 hours | 
| narcotic usage |  | 64 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, ropivacaine, infusion, sternotomy