Ketamine In Thoracic Surgery (KITS) Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00504725
First received: July 18, 2007
Last updated: November 14, 2012
Last verified: November 2012
  Purpose

The primary aim of the study is to demonstrate a reduction in circulating interleukin 6 levels at 4 and 24 hours after completion of lobectomy (either VATS or open). The null hypothesis (H0) is thus that there is no difference in circulating interleukin 6 levels when patients are given either ketamine or placebo (0.9% saline in equivalent volume). The alternative (two tailed) hypothesis (HA) if the null is disproved is that ketamine leads to significantly different levels of interleukin 6 at 4 and 24 hours after completion of 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.


Condition Intervention Phase
Lung Cancer
Drug: Ketamine
Drug: 0.9% saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine In Thoracic Surgery (KITS) Trial

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Interleukin Levels at 24 Hours [ Time Frame: 24 Hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • C-reactive Protein (CRP) Serum Levels [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The CRP levels were measured 24 hours postoperatively.

  • Verbal Pain Scores [ Time Frame: baseline, 4 hours, 24 hours and at discharge ] [ Designated as safety issue: No ]
    Pain scores rated by the subject on a scale of 0 low - 10 high


Enrollment: 40
Study Start Date: July 2007
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
Single bolus 0.5mg/kg ketamine IV after induction of anesthesia
Drug: Ketamine
Interventional
Placebo Comparator: Placebo
0.9 % saline bolus of equivalent volume
Drug: 0.9% saline
placebo

Detailed Description:

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.
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients presenting for lobectomy either VATS or open.

Exclusion Criteria:

  • Patients with myocardial infarction in the previous six months,
  • Patients with a history of psychotic disorder,
  • Patients with a history of chronic pain syndrome,
  • Patients with documented previous allergy to ketamine.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504725

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Andy Shaw, M. D. Duke University
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00504725     History of Changes
Other Study ID Numbers: Pro00000895
Study First Received: July 18, 2007
Results First Received: September 29, 2011
Last Updated: November 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Lobectomy
VATS

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Ketamine
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 08, 2014