KPSF: Low Dose Ketamine Study on Opioid Tolerance and Hyperalgesia

• Sponsor: Julia Finkel (Other)
• Overall Status: Completed
• CT.gov ID: NCT01325493
• Collaborator: (none)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to:

1. Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Scoliosis; Spondylolisthesis	Drug: Ketamine; Drug: Normal Saline	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Modulation of μ Opioid Receptor Mediated Analgesia, Tolerance and Hyperalgesia in Children and Adolescents
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Normal Saline Normal Saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h	Drug: Normal Saline; Normal saline given 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h; Other Names: 0.90% NaCl
Active Comparator: Ketamine ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h	Drug: Ketamine; ketamine 0.5mg/kg intravenous (IV) load followed by an intraoperative continuous infusion at 0.25mg/kg/h and a postoperative infusion at 0.1mg/kg/h; Other Names: Ketanest, Ketaset, and Ketalar

Outcome Measures

Primary Outcome Measures

1. Morphine Equivalent Consumption (mg/kg) [at 24, 48, 72, 96 hours post operatively]

   Morphine consumption (mg/kg) was measured over time in the Ketamine group and compared to the Control (saline) group. Values are for each 24 hour time period and displayed as hours post surgery.

Secondary Outcome Measures

1. Sedation Score [24, 48, 72, 96 hours post operatively]

   Sedation scores 0 = completely awake = sleepy but responds appropriately = somnolent but arouses to light stimuli = asleep but responsive to deeper physical stimuli = asleep and not responsive to any stimuli Values are for each 24 hour time period and displayed as hours post surgery.

2. Pain Score at Rest [24, 48, 72, 96 hours post operatively]

   Patient volunteered response at rest, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.

3. Pain Score During Cough. [24, 48, 72, 96 hours post operatively]

   Patient volunteered response during a cough, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The subject is 10 to 18 years of age

2. The subject's American Society of Anesthesiologists physical status is ASA 1, 2 or 3 (see appendix I)

3. The subject is scheduled for elective posterior spinal fusion and instrumentation.

4. The subject's parent/legally authorized guardian has given written informed consent to participate

Exclusion Criteria:

1. The subject has a history or a family (parent or sibling) history of malignant hyperthermia

2. The subject is pregnant or nursing.

3. The subject has known significant renal disorders determined by medical history, physical examination or laboratory tests

4. The subject has a known or suspected allergy to morphine, remifentanil or ketamine

5. The subject is an ASA classification of 4 or greater (See Appendix I)

6. The subject is scheduled for a surgical sub-procedure (i.e. anterior spinal fusion)

7. The subject is unable to self-administer morphine using patient-controlled analgesia (PCA) pump

8. The subject had a recent opioid exposure (within 1 month of surgery)

9. The subject is obese (body mass index >30kg/m2)

10. The subject is planned for elective postoperative ventilation

11. The subject has a known ocular disease not permitting pupillometric examination

12. The subject has used any investigation products in the past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010

Sponsors and Collaborators

• Julia Finkel

Investigators

• Principal Investigator: Pestieau Sophie, MD, Children's National Research Institute
• Study Director: Finkel C Julie, MD, Children's National Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Julia Finkel, Director of Research, Children's National Research Institute
• ClinicalTrials.gov Identifier: NCT01325493
• Other Study ID Numbers: 4735
• First Posted: Mar 29, 2011
• Last Update Posted: Jan 14, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by Julia Finkel, Director of Research, Children's National Research Institute: opioid tolerance; hyperalgesia; scoliosis; pupillometry
• Additional relevant MeSH terms: Scoliosis; Spondylolisthesis; Hyperalgesia; Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine	Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
Period Title: Overall Study
STARTED	30	24
COMPLETED	29	21
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Ketamine	Saline	Total
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Total of all reporting groups
Overall Participants	29	21	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	14	14	14
Sex: Female, Male (Count of Participants)
Female	24 82.8%	14 66.7%	38 76%
Male	5 17.2%	7 33.3%	12 24%
Region of Enrollment (participants) [Number]
United States	29 100%	21 100%	50 100%
American Society of Anesthesiology classification (participants) [Number]
ASA 1	13 44.8%	14 66.7%	27 54%
ASA 2	15 51.7%	7 33.3%	22 44%
ASA 3	1 3.4%	0 0%	1 2%

Outcome Measures

1. Primary Outcome

Title	Morphine Equivalent Consumption (mg/kg)
Description	Morphine consumption (mg/kg) was measured over time in the Ketamine group and compared to the Control (saline) group. Values are for each 24 hour time period and displayed as hours post surgery.
Time Frame	at 24, 48, 72, 96 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
Measure Participants	29	21
24 hrs after surgery	1.3 (.3)	1.36 (.42)
48 hrs after surgery	1.28 (.26)	1.275 (.31)
72 hrs after surgery	.89 (.55)	.93 (.36)
96 hrs after surgery	.57 (.44)	.38 (.35)

2. Secondary Outcome

Title	Sedation Score
Description	Sedation scores 0 = completely awake = sleepy but responds appropriately = somnolent but arouses to light stimuli = asleep but responsive to deeper physical stimuli = asleep and not responsive to any stimuli Values are for each 24 hour time period and displayed as hours post surgery.
Time Frame	24, 48, 72, 96 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
Measure Participants	29	21
24 hrs after surgery	.73 (.68)	.75 (.73)
48 hrs after surgery	.62 (.8)	.54 (.85)
72 hrs after surgery	.38 (.45)	.3 (.84)
96 hrs after surgery	.24 (.43)	.21 (.39)

3. Secondary Outcome

Title	Pain Score at Rest
Description	Patient volunteered response at rest, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.
Time Frame	24, 48, 72, 96 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
Measure Participants	29	21
24 hrs after surgery	3.9 (2.1)	4.55 (2.0)
48 hrs after surgery	4.53 (1.69)	5.2 (2.2)
72 hrs after surgery	3.6 (2.3)	3.48 (2.0)
96 hrs after surgery	4.48 (2.1)	3.8 (1.8)

4. Secondary Outcome

Title	Pain Score During Cough.
Description	Patient volunteered response during a cough, 1-10 scale (where a higher score indicates more pain and a lower score indicates less pain). Values are for each 24 hour time period and displayed as hours post surgery.
Time Frame	24, 48, 72, 96 hours post operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.	Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
Measure Participants	29	21
24 hrs after surgery	4.5 (2.5)	5.1 (3.0)
48 hrs after surgery	5.4 (2.3)	5.45 (2.7)
72 hrs after surgery	4.4 (2.3)	3.7 (2.5)
96 hrs after surgery	5.15 (2.5)	4.2 (2)

Adverse Events

Time Frame	the duration of the study (96 hrs) post surgery
Arm/Group Title	Ketamine		Saline
Arm/Group Description	Ketamine was diluted in 50mL of normal saline to a concentration of 10 mg*ml-1, administered by the anestheisologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.		Normal saline was administered by the anesthesiologist (blind) via IV using a loading dose of 0.5 mg/kg-1, intra-operatively 0.25 mg/kg/hr-1, post-operatively 0.1 mg/kg/hr-1.
All Cause Mortality
	Ketamine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketamine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/21 (0%)
Surgical and medical procedures
Allergy	1/29 (3.4%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Ketamine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/21 (0%)

Limitations/Caveats

Patient sex and ethnicity could have led to analytical bias.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.