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Low Dose Ketamine and Acute Pain Crisis (LDK-SCD)

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ClinicalTrials.gov Identifier: NCT04330183
Recruitment Status : Recruiting
First Posted : April 1, 2020
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Rhode Island Hospital

Tracking Information
First Submitted Date  ICMJE March 23, 2020
First Posted Date  ICMJE April 1, 2020
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE July 1, 2020
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
Pain intensity [ Time Frame: 4 hours ]
We anticipate a decrease in numeric pain score after ketamine administration
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
Emergency department length of stay [ Time Frame: 4 hours ]
We anticipate a decrease in the LOS in the ED
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low Dose Ketamine and Acute Pain Crisis
Official Title  ICMJE Low Dose Ketamine for Acute Pain Crisis in Patients With Sickle Cell Disease
Brief Summary

BACKGROUND:

Current treatment standard for acute pain crisis in sickle cell disease (SCD) is largely supportive care: opioid analgesics, hydration, oxygen, and blood transfusion. Sickle cell disease (SCD) is a chronic condition associated with serious and disabling acute consequences such as a vaso-occlusive (VOC) or pain crisis. Uncontrolled pain is the hallmark of a VOC, and often results in acute unscheduled care in the patient's clinic or hospital emergency department (ED). During these pain crises, patients sometimes require high doses of opioids for analgesia. Opioid analgesics are fraught with challenges including the development of tolerance, dependence, and opioid-induced hyperalgesia (whereby the use of opioids actually makes patients more sensitive to pain). Finding non-opioid alternatives for intravenous analgesia is problematic based on the limited availability this class of drugs. Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor antagonist that even at low doses has demonstrated efficacy as an adjunct to opioids for acute pain control.

OBJECTIVE:

The investigators will determine the comparative efficacy of low doses of ketamine as an adjunct to opioids versus standard care (opioids alone) for the treatment of acute severe pain in patients with sickle cell related pain crisis.

METHODS:

The investigators propose a double-blinded, randomized, placebo-controlled pilot study to determine the efficacy of ketamine 0.3mg/kg vs. placebo for the treatment of acute pain crisis. The investigators will include all eligible emergency department ≥18 years. The investigators will stratify 42 patients by location, 21 patients per site. Numeric Rating Scale (NRS) will be recorded as a part of the study log at 0, 1, 2 and 3hrs after the study drug administration.

HYPOTHESIS:

The investigators hypothesize that the ketamine will decrease overall pain intensity, visit length of stay, and hospitalizations.

Detailed Description

Current treatment standard for acute pain crisis in sickle cell disease (SCD) is largely supportive care: opioid analgesics, hydration, oxygen, and blood transfusion. Sickle cell disease (SCD) is a chronic condition associated with serious and disabling acute consequences such as a vaso-occlusive (VOC) or pain crisis. Uncontrolled pain is the hallmark of a VOC, and often results in acute unscheduled care in the patient's clinic or hospital emergency department (ED). The pain associated with acute VOC in sickle cell disease is caused by the change in the structure of red blood cells. This change leads to microvascular obstruction, a decrease in laminar blood flow, diminished tissue oxygen exchange, and ultimately microenvironmental changes resulting in severe pain.1 During these pain crises, patients sometimes require high doses of opioids for analgesia. Poor pain control, in the setting of high dose opioid administration, is the most common reason for a patient to be hospitalized with acute VOC. Opioid analgesics are fraught with challenges including the development of tolerance, dependence, and opioid-induced hyperalgesia (whereby the use of opioids actually makes patients more sensitive to pain). Finding non-opioid alternatives for intravenous analgesia is problematic based on limited availability and poor side-effect profile. One alternative suggested for use in patients with VOC is ketamine, a potent N-methyl-D-aspartate (NMDA) antagonist.

The current evidence suggests that the counterintuitive effects of opioids are related to activation of NMDA receptors. These effects may be more pronounced in patients with sickle cell disease, as approximately half of these patients have chronic pain and are on long term opioids. The NMDA receptor is activated in response to injury of inflammation, precipitating heightening pain perception, and is therefore an important analgesic target for patients receiving opioids. Ketamine is a potent NMDA receptor antagonist that even at low doses has demonstrated efficacy as an adjunct to opioids for acute pain control. Multiple emergency department studies have shown that low doses of ketamine, <1mg/kg, provides analgesic effects, decreases pain scores, and decreases total opioid use.2-4 While these studies do not focus specifically on adult patients with SCD, ketamine has shown promise in similar pediatric populations. Unfortunately, there are no high-quality studies examining ketamine usage in adult patients with SCD, making highly addictive opioid medications the standard for pain relief during a crisis. The goal of this study is to determine the effectiveness of one non-opioid analgesic, ketamine, in the treatment of acute pain in a vulnerable patient population.

PRIMARY AIM: The investigators will determine the comparative efficacy of low doses of ketamine as an adjunct to opioids versus standard care (opioids alone) for the treatment of acute severe pain in patients with sickle cell related pain crisis. The investigators propose a double-blinded, randomized, placebo-controlled pilot study. The primary outcome will be assessed by patient-reported pain intensity and use of rescue opioid analgesia. Adverse events, length of the encounter, and hospitalization will be evaluated as secondary outcomes. Our central hypothesis is that the ketamine will decrease overall pain intensity, visit length of stay, and hospitalizations. The investigators will enroll patients at both a community hospital emergency department and a tertiary care, academic center. Both locations evaluate and treat patients with acute VOC and will provide an adequate volume for this pilot trial. At the end of this study the investigators expect to determine the effectiveness of ketamine in the treatment of acute pain in patients with SCD presenting after a VOC. Our team is composed of physician-scientists, competent and confident in conducting both clinical and methodological aspects of the trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Crisis
Intervention  ICMJE
  • Drug: Ketamine
    0.3mg/kg of ketamine
  • Drug: Normal Saline
    3cc of normal saline
Study Arms  ICMJE
  • Placebo Comparator: Normal Saline
    Patients here will be administered 3cc of normal saline as placebo
    Intervention: Drug: Normal Saline
  • Experimental: Ketamine Interventions
    Patients will be administered weight based 0.3mg/kg of ketamine
    Intervention: Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 31, 2020)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All English-speaking adult patients >=18yrs old patients presenting with acute pain crisis

Exclusion Criteria:

  • Inability to provide consent,
  • Allergy to ketamine
  • Pregnant or breastfeeding. W
  • Signs and symptoms of intracranial hypertension
  • Neurologic deficits
  • Headache only
  • Temperature >102F
  • Sustained blood pressure >=180/110
  • Sustained heart rate >130
  • Current priapism
  • Patients requiring a blood transfusion at the time of acute presentation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Taneisha Wilson, MD, ScM 401.444.5027 taneisha_wilson@brown.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04330183
Other Study ID Numbers  ICMJE 1481617
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan at this time to share IPD with other researchers.
Responsible Party Rhode Island Hospital
Study Sponsor  ICMJE Rhode Island Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Taneisha Wison, MD, ScM Brown Emergency Medicine
PRS Account Rhode Island Hospital
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP