Randomized Controlled Trial of Ketamine Infusion With Continuous Epidural Infusion for Treatment of Complex Regional Pain Syndrome

• Sponsor: Hospital for Special Surgery, New York (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02094352
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether epidural and ketamine infusions are effective in the treatment of Complex Regional Pain Syndrome (CRPS).

Condition or Disease	Intervention/Treatment	Phase
Complex Regional Pain Syndrome	Drug: Ketamine Infusion + Epidural Infusion; Drug: Control Group + Epidural infusion; Drug: Ketamine Booster Infusion; Drug: Control Group Booster Infusion	Phase 2

Detailed Description

Potential patients must clear all study requirements to be enrolled. Study requirements include labwork, psychiatric evaluation, and cardiology evaluation.

Once enrolled, patients will be in one of two groups:

1. Receives epidural infusion

2. Receives epidural and ketamine infusions

The patient and study staff are blinded.

This study requires multiple visits to Hospital for Special Surgery in New York City over the course of three months and concludes with a final visit after six months. The study will only cover costs associated with the scheduled in-patient and out-patient visits. The study patient will be responsible for all other costs (including travel and hotel accommodations) that he/she may incur for participating in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Subanesthetic Intravenous Ketamine Infusion in Conjunction With Continuous Epidural Infusion for Treatment of Refractory Complex Regional Pain Syndrome
• Actual Study Start Date: Mar 24, 2014
• Actual Primary Completion Date: Apr 20, 2015
• Actual Study Completion Date: Apr 20, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine Infusion + Epidural Infusion + Booster Infusion Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of KETAMINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three ketamine booster infusions over the course of three months.	Drug: Ketamine Infusion + Epidural Infusion; The ketamine and epidural infusions will be administered over 96 hours with appropriate titration.; Other Names: Ketamine Epidural ; Drug: Ketamine Booster Infusion; Patients will receive three ketamine booster infusions over the course of three months.; Other Names: Ketamine
Placebo Comparator: Control Group + Epidural Infusion + Booster Infusion Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of SALINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three saline booster infusions over the course of three months.	Drug: Control Group + Epidural infusion; The saline and epidural infusions will be administered over 96 hours with appropriate titration.; Other Names: Epidural ; Drug: Control Group Booster Infusion; Patients will receive three saline booster infusions over the course of three months.; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Pain Reduction [6 months post infusion]

   Evidence of changes in NRS pain scores between baseline and six months post infusion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

INCLUSION CRITERIA:

• Patients must meet the Budapest CRPS criteria, including two or more symptom categories and three or more sign categories (as previously documented by a pain management physician or neurologist, or as observed on initial neurologic examination by the study investigator)

• Patients must have trialed at least three of the following therapies without relief judged adequate by the patient:

• Anti-depressants

• Anti-seizure medication

• Muscle relaxants

• Nerve blocks (somatic or sympathetic)

• Non-opioid analgesics

• Non-steroidal anti-inflammatory drugs

• Opioid analgesics

• Physical therapy

• Spinal cord stimulator trial

• Patients of either gender between the ages of 18 and 65 inclusive

• Patient report of a NRS pain score of at least 5 in at least two out-patient pain management physician clinic visits

EXCLUSION CRITERIA:

• Patients younger than 18 or older than 65

• Patients who:

• Are pregnant

• Are affected with glaucoma

• Are affected with thyrotoxicosis

• Are lactating

• Are on chronic anticoagulation therapy

• Have autonomic dysfunction with hemodynamic instability

• Have cardiac rhythm disturbance

• Have cerebrovascular disease

• Have conditions that would preclude central line placement

• Have conditions that would preclude epidural catheter placement

• Have congestive heart failure

• Have coronary artery disease

• Have creatinine level above 1.5

• Have electrolyte disturbance

• Have had previous reaction to IV contrast dye

• Have history of deep vein thrombosis

• Have history of systemic administration of ketamine for the treatment of pain

• Have liver disease

• Have known history of psychosis, significant thought disorder, or untreated (bipolar disorder depression or anxiety disorder ok)

• Have uncontrolled hypertension

• Any patient who is unable to provide consent due to cognitive difficulties

• Non-English speakers, as some of the instruments are only validated in English

• Patients with active litigation or workers compensation related to CRPS

• Patients with an intolerance or allergy to any medication planned as a component of the study

• Patients with known history of illegal drug use or alcohol dependence

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital for Special Surgery	New York	New York	United States	10021

Sponsors and Collaborators

• Hospital for Special Surgery, New York

Investigators

• Principal Investigator: Daniel I Richman, MD, Hospital for Special Surgery, New York

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hospital for Special Surgery

Publications

None provided.

• Responsible Party: Hospital for Special Surgery, New York
• ClinicalTrials.gov Identifier: NCT02094352
• Other Study ID Numbers: 2013-003
• First Posted: Mar 21, 2014
• Last Update Posted: Jan 31, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Hospital for Special Surgery, New York: Complex Regional Pain Syndrome; Pain management; Ketamine infusion
• Additional relevant MeSH terms: Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Syndrome; Somatoform Disorders; Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine Infusion + Epidural Infusion + Booster Infusion	Control Group + Epidural Infusion + Booster Infusion
Arm/Group Description	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of KETAMINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three ketamine booster infusions over the course of three months. Ketamine Infusion + Epidural Infusion: The ketamine and epidural infusions will be administered over 96 hours with appropriate titration. Ketamine Booster Infusion: Patients will receive three ketamine booster infusions over the course of three months.	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of SALINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three saline booster infusions over the course of three months. Control Group + Epidural infusion: The saline and epidural infusions will be administered over 96 hours with appropriate titration. Control Group Booster Infusion: Patients will receive three saline booster infusions over the course of three months.
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ketamine Infusion + Epidural Infusion + Booster Infusion	Control Group + Epidural Infusion + Booster Infusion	Total
Arm/Group Description	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of KETAMINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three ketamine booster infusions over the course of three months. Ketamine Infusion + Epidural Infusion: The ketamine and epidural infusions will be administered over 96 hours with appropriate titration. Ketamine Booster Infusion: Patients will receive three ketamine booster infusions over the course of three months.	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of SALINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three saline booster infusions over the course of three months. Control Group + Epidural infusion: The saline and epidural infusions will be administered over 96 hours with appropriate titration. Control Group Booster Infusion: Patients will receive three saline booster infusions over the course of three months.	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	1 100%	2 66.7%
Male	1 50%	0 0%	1 33.3%

Outcome Measures

1. Primary Outcome

Title	Pain Reduction
Description	Evidence of changes in NRS pain scores between baseline and six months post infusion
Time Frame	6 months post infusion

Outcome Measure Data

Analysis Population Description

Study terminated early due to lack of enrollment. We did not analyze any data.

Arm/Group Title	Ketamine Infusion + Epidural Infusion + Booster Infusion	Control Group + Epidural Infusion + Booster Infusion
Arm/Group Description	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of KETAMINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three ketamine booster infusions over the course of three months. Ketamine Infusion + Epidural Infusion: The ketamine and epidural infusions will be administered over 96 hours with appropriate titration. Ketamine Booster Infusion: Patients will receive three ketamine booster infusions over the course of three months.	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of SALINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three saline booster infusions over the course of three months. Control Group + Epidural infusion: The saline and epidural infusions will be administered over 96 hours with appropriate titration. Control Group Booster Infusion: Patients will receive three saline booster infusions over the course of three months.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Ketamine Infusion + Epidural Infusion + Booster Infusion		Control Group + Epidural Infusion + Booster Infusion
Arm/Group Description	Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of KETAMINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three ketamine booster infusions over the course of three months. Ketamine Infusion + Epidural Infusion: The ketamine and epidural infusions will be administered over 96 hours with appropriate titration. Ketamine Booster Infusion: Patients will receive three ketamine booster infusions over the course of three months.		Inpatient: Patients will receive a subanesthetic continuous intravenous infusion of SALINE 500mg/500ml in 0.9% Sodium Chloride with an epidural infusion. Outpatient: Patients will receive three saline booster infusions over the course of three months. Control Group + Epidural infusion: The saline and epidural infusions will be administered over 96 hours with appropriate titration. Control Group Booster Infusion: Patients will receive three saline booster infusions over the course of three months.
All Cause Mortality
	Ketamine Infusion + Epidural Infusion + Booster Infusion		Control Group + Epidural Infusion + Booster Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketamine Infusion + Epidural Infusion + Booster Infusion		Control Group + Epidural Infusion + Booster Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine Infusion + Epidural Infusion + Booster Infusion		Control Group + Epidural Infusion + Booster Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.