Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04330183 |
| Other study ID # |
1481617 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
October 1, 2021 |
Study information
| Verified date |
December 2021 |
| Source |
Rhode Island Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
