Trial Information

Ketamine In Thoracic Surgery (KITS) Trial

This study is designed to be a phase 2 (efficacy) randomized controlled clinical trial of
ketamine versus placebo in 40 patients undergoing lobectomy by VATS or open approach, at
Duke University. We selected a single dose regimen of 0.5mg/kg IV ketamine given at
induction of anesthesia, as this is the dose that previously has been shown to induce
maximal suppression of the IL-6 response in cardiac surgery.

We plan to randomize 40 patients to receive either ketamine or placebo, in a block of 4
randomization design stratified by whether surgery is performed by VATS or open lobectomy.
40 patients (n=20 per group) will provide 90% power to detect a change in IL 6 of 20 pg/ml
from a mean of 100 pg/ml at 4 hours, with two tailed alpha = 0.05. Allowing for 10-20%
attrition we will enroll 50 patients to achieve this sample size. All patients presenting
for lobectomy either VATS or open will be included. Patients will be screened by review of
the preoperative surgical schedule posted each day and approached for consent to participate
if they do not have any exclusion criteria. Patients who are randomized but do not undergo
lobectomy for any reason will not be included in the analysis of the primary endpoint.
Patients who are listed for VATS resection but convert to open will be included in the
analysis on a per protocol basis. The randomization is stratified according to planned
approach (VATS vs open), however we expect the majority of these cases to be VATS
lobectomies.

Treatment will be by intravenous administration of a single dose of study drug over 5
minutes immediately after induction of anesthesia and before surgical incision.

Patients will be randomized (by sealed envelope) in blocks of 4 to receive ketamine or
placebo. The randomization will be stratified according to whether the planned surgery is
via VATS or open (thoracotomy) approach. The study drug will be prepared by the
investigational pharmacy and provided to the attending anesthesiologist of record for the
case. It will contain 0.5 mg/kg ketamine for injection by IV bolus over 5 minutes, or as an
equivalent volume of 0.9% saline. It will be the responsibility of the principal
investigator to ensure that study drug is administered in a timely fashion, usually by
delegation to the attending anesthesiologist of record for the case. The anesthetic
procedure will be standardized in that each patient will receive a total intravenous
anesthetic using propofol and an intravenous opioid infusion. This anesthetic will be
supplemented by an epidural and intravenous opioid boluses as needed to control pain.

Visits by the research team will be performed as follows:

1. Visit 1 will occur at enrollment, when baseline information (see CRF visit 1) will be
collected and study consent forms signed.

2. Visit 2 will occur at induction of anesthesia when study drug will be administered and
a baseline blood sample of 10ml collected from the patient's arterial line. The blood
sample will be immediately centrifuged and the serum frozen and stored for subsequent
analysis.

3. Visit 3 will occur at 4 hours after completion of surgery when 10 ml blood will be
collected and CRF visit 3 form will be completed (VAS score and emergence delirium).

4. Visit 4 will occur at 24 hours after completion of surgery when 10 ml blood will be
collected and CRF visit 4 form will be completed (VAS score).

5. The final visit will occur just prior to hospital discharge when CRF visit 5 form will
be completed (secondary endpoints). Additionally, if the principal investigator is
informed by either study staff or the clinical team of an adverse event or other
complication, then the patient will be visited within 24 hours for confirmation of the
event and ascertainment of whether the event is related to study drug or not. An SAE
form will be completed and sent to the IRB in line with institutional policy.