Trial Outcomes & Findings for Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis (NCT NCT03296345)

Last Updated: 2021-04-20

Results Overview

The number of serious and minor adverse events was measured via patient-completed survey as well as by nurse and medical providers on presentation to the emergency department (ED). Serious adverse events are defined as cardiorespiratory events requiring intervention. Minor adverse events are defined as nausea/vomiting, emergence reaction (dysphoria; hallucinations; frightening dreams), and a sense of de-realization or "dreamy" sensation. Both study providers and patients themselves, via a survey that the parent and/or patient (based on age) fills out post receipt of ketamine, reported serious and minor adverse events.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

18 months

Results posted on

2021-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	Study Participants Intervention: Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study. Historical Control: Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Overall Study STARTED	62
Overall Study COMPLETED	62
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Adjuvant Low-dose Ketamine in Pediatric Sickle Cell Vaso-occlusive Crisis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Participants n=62 Participants Intervention: Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention is IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs).
Age, Continuous	18.1 years n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	61 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Site of pain on presentation Back	22 participants n=5 Participants
Site of pain on presentation Extremity	16 participants n=5 Participants
Site of pain on presentation Chest	12 participants n=5 Participants
Site of pain on presentation Whole body	5 participants n=5 Participants
Site of pain on presentation Abdomen	4 participants n=5 Participants
Site of pain on presentation Other	3 participants n=5 Participants
Site of pain on presentation Unknown	0 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Serious adverse events	0 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Nausea/vomiting	4 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Emergence of emergence-like symptoms	4 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Dream-like/de-realized sensation	26 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Blurry vision	3 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Dizziness	2 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Floating sensation	1 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Heavy sensation	1 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] Dry mouth	1 Participants	—
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] No adverse event	20 Participants	—

SECONDARY outcome

Timeframe: Up to one year prior and after LDK administration on day 1 of the study in the ED

Population: 62 enrolled patient-encounters were compared to their prior visits individually. At least one but up to three prior visits were averaged and compared to the intervention visit.

Opioid usage for at least one but up to three prior patient visits in the last one year for each patient enrolled in the study was summarized, expressed as morphine equivalents in mg/kg/h, to account for different types of opioids used per patient preference, and then this was compared to the intervention group that received LDK. Percent change in opioid usage (expressed as morphine equivalents in mg/kg/h) is reported).

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine (LDK) on Opioid Usage in the ED	-15 percent change Interval -28.0 to -2.3	—

SECONDARY outcome

Timeframe: Up to one year prior and on presentation to the ED after LDK administration

Patient pain scores at presentation for the enrolled encounters and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control n=62 Participants Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine on Pain Scores on Presentation to the ED	9.23 Score on a scale Interval 8.98 to 9.47	9.08 Score on a scale Interval 8.83 to 9.34

SECONDARY outcome

Timeframe: Up to one year prior to receipt of ketamine for the historical control arm/group and up to 18 months for the intervention arm/group

Percent discharge from the ED for intervention group and for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. Participants were assigned a "0" if discharged or "1" if not discharged.

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control n=62 Participants Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine on Discharge Rates From the ED	33 percentage of participants	17 percentage of participants

SECONDARY outcome

Timeframe: after LDK administration on day 1 of the study in the ED

After receipt of LDK, patients and/or their parents, based on age, filled out a survey based on a Likert scale regarding their agreement (Strongly Disagree to Strongly Agree) with the following statements: Achieved faster pain relief with LDK, Achieved more complete pain relief with LDK, and Desire to receive LDK in a future vaso-occlusive crisis. There is also an area where patients could provide general comments regarding their experience in receiving LDK. Count of Participants who agree or strongly agree for each question are reported.

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey Achieved faster pain relief?	43 Participants	—
Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey Achieved more complete pain relief?	30 Participants	—
Subjective Effect of Low Dose Ketamine on Pain Relief Assessed Via a Patient Survey Desire to receive LDK in the future?	49 Participants	—

SECONDARY outcome

Timeframe: At time of discharge from the ED/admission to the hospital (up to one year prior and after LDK administration)

Patient pain scores at time of discharge from the ED/admission to the hospital for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed. At least one but up to three prior visits were averaged and compared to the intervention visit. Pain scores post receipt of ketamine are presented for the intervention group. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control n=62 Participants Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine on Patient Pain Scores on Discharge From the ED/Admission to the Hospital	7.15 Score on a scale Interval 6.61 to 7.68	7.26 Score on a scale Interval 6.84 to 7.68

SECONDARY outcome

Timeframe: Up to one year prior to and after LDK administration on day 1 of the study in the ED

Length of stay (LOS) in minutes in the ED for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed.

Outcome measures

Outcome measures
Measure	Intervention n=62 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control n=62 Participants Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine on Percent Difference of Length of Stay (LOS) in the ED	273.5 LOS in minutes Interval 241.3 to 305.6	217.3 LOS in minutes Interval 200.0 to 234.5

SECONDARY outcome

Timeframe: Up to one year prior to and after LDK administration on day 1 of the study in the ED

Population: 16 participants reported a 50% pain reduction, and those 16 participants were included in the analysis of time to 50% pain reduction.

Time to 50% pain reduction (pain reported 50% less than baseline) in minutes for at least one but up to three visits prior to receipt of ketamine in the last one year, were assessed as historical controls. Pain was assessed using the faces pain scale which consists of a series of line diagrams of faces with expressions of increasing distress. The score ranges from 0 (no pain) to 10 (the worst pain).

Outcome measures

Outcome measures
Measure	Intervention n=16 Participants Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.	Historical Control n=16 Participants Patient data from at least one but up three patient encounters within the prior year were compared to their visit in which they were given adjuvant ketamine, using the outcome measures in the "Intervention" arm. Since this a historical control study, patients acted as their own controls in the above manner. Patients were allowed to re-enroll 4 weeks after presentation, which is typically considered a separate vaso-occlusive episode in the literature.
Effect of Low-dose Ketamine on Time to 50% Pain Reduction	116.1 time to 50% pain reduction in minutes Interval 111.6 to 220.6	167.3 time to 50% pain reduction in minutes Interval 117.0 to 217.5

Adverse Events

Intervention

Serious events: 0 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intervention n=62 participants at risk Prior to the second dose of IV opiates, the experiment was to give patients a single IV bolus of ketamine at the dose of 0.2 mg/kg. Ketamine: The intervention was IV low-dose bolus ketamine as an adjuvant to standard therapy (IV opiates and NSAIDs). Ultimately, 62 patient encounters were enrolled in the study.
Gastrointestinal disorders Nausea/vomiting	6.5% 4/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
General disorders Emergence of emergence-like symptoms	6.5% 4/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
General disorders Dream-like/de-realized sensation	41.9% 26/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
Eye disorders Blurry vision	4.8% 3/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
Vascular disorders Dizziness	3.2% 2/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
General disorders Floating sensation	1.6% 1/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
General disorders Heavy sensation	1.6% 1/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.
General disorders Dry mouth	1.6% 1/62 • 18 months Serious adverse events were defined per protocol as reaction to intervention causing cardiorespiratory compromise requiring medical intervention.

Additional Information

Jonathan Bryan Cooper-Sood, MD

Valley Children's Hospital

Phone: 559-353-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place