Trial Outcomes & Findings for Low-dose Ketamine vs Morphine for Vaso-occlusive Crisis in Sicklers (NCT NCT02434939)
NCT ID: NCT02434939
Last Updated: 2016-08-03
Results Overview
Our primary outcome measurement was the maximum change on the verbal NRS pain scale compared with their initial score (baseline). The NRS was used to measure a patient's subjective level of pain on a scale from 0 (representing no pain at all) to 10 (the worst pain imaginable) using whole numbers. The NRS score was documented just prior to the administration of the study drug (time zero). After infusion of the study drug was complete, NRS scores were documented at 5, 10, 20, and then every 20 minutes thereafter up to 120 minutes. We stopped recording NRS scores prior to 120 minutes if the patient requested a third dose of the study drug, withdrew consent or developed a severe adverse effect.
COMPLETED
PHASE4
240 participants
5, 10, 20,25,30, 40,45,50 60, 80, 100, 120 minutes post drug adminstration
2016-08-03
Participant Flow
This study enrolled children with SCD aged 7-18 with severe acute VOC admitted to the Sickle cell day care center at Mulago National Refferal Hospital from June 2015 to February 2016
Of the 800 patients, 314 met the inclusion criteria with a further 74 excluded. these included 28 with history stroke, 17 with SPO2 \< 90, 14 declined, 2 had altered mentation and 13 had undisclosed reasons. only 240 patients were randomized.
Participant milestones
| Measure |
Low Dose Ketamine
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Overall Study
STARTED
|
120
|
120
|
|
Overall Study
COMPLETED
|
83
|
71
|
|
Overall Study
NOT COMPLETED
|
37
|
49
|
Reasons for withdrawal
| Measure |
Low Dose Ketamine
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
34
|
48
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
Low-dose Ketamine vs Morphine for Vaso-occlusive Crisis in Sicklers
Baseline characteristics by cohort
| Measure |
Low Dose Ketamine
n=120 Participants
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=120 Participants
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Total
n=240 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
11.8 years
STANDARD_DEVIATION 3.4 • n=93 Participants
|
11.8 years
STANDARD_DEVIATION 3.6 • n=4 Participants
|
11.8 years
STANDARD_DEVIATION 3.5 • n=27 Participants
|
|
Sex: Female, Male
Female
|
77 Participants
n=93 Participants
|
78 Participants
n=4 Participants
|
155 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=93 Participants
|
42 Participants
n=4 Participants
|
85 Participants
n=27 Participants
|
|
Weight
|
30.8 kgs
STANDARD_DEVIATION 11.9 • n=93 Participants
|
30.0 kgs
STANDARD_DEVIATION 12.2 • n=4 Participants
|
30.4 kgs
STANDARD_DEVIATION 12.1 • n=27 Participants
|
|
Medication
prior medication
|
31 participants
n=93 Participants
|
42 participants
n=4 Participants
|
73 participants
n=27 Participants
|
|
Medication
no prior medication
|
89 participants
n=93 Participants
|
78 participants
n=4 Participants
|
167 participants
n=27 Participants
|
|
Numerical Rating Scale (NRS) pain score
|
8.9 units on a scale
STANDARD_DEVIATION 1.2 • n=93 Participants
|
9.2 units on a scale
STANDARD_DEVIATION 1.0 • n=4 Participants
|
9.1 units on a scale
STANDARD_DEVIATION 1.1 • n=27 Participants
|
|
Temperature
|
36.7 oC
STANDARD_DEVIATION 0.86 • n=93 Participants
|
36.8 oC
STANDARD_DEVIATION 0.74 • n=4 Participants
|
36.8 oC
STANDARD_DEVIATION 0.8 • n=27 Participants
|
|
blood pressure
systolic
|
113.7 mmHg
STANDARD_DEVIATION 14.0 • n=93 Participants
|
115.2 mmHg
STANDARD_DEVIATION 15.7 • n=4 Participants
|
114.4 mmHg
STANDARD_DEVIATION 14.9 • n=27 Participants
|
|
blood pressure
diastolic
|
64.7 mmHg
STANDARD_DEVIATION 12.3 • n=93 Participants
|
65.2 mmHg
STANDARD_DEVIATION 14.1 • n=4 Participants
|
65 mmHg
STANDARD_DEVIATION 13.2 • n=27 Participants
|
|
Heart rate
|
95.8 bpm
STANDARD_DEVIATION 15.8 • n=93 Participants
|
98.8 bpm
STANDARD_DEVIATION 17.8 • n=4 Participants
|
97.3 bpm
STANDARD_DEVIATION 16.8 • n=27 Participants
|
|
SPO2
|
93.9 percentage of oxygen saturation
STANDARD_DEVIATION 4.8 • n=93 Participants
|
94.7 percentage of oxygen saturation
STANDARD_DEVIATION 3.4 • n=4 Participants
|
94.3 percentage of oxygen saturation
STANDARD_DEVIATION 4.1 • n=27 Participants
|
|
respiratory rate
|
23.8 breaths/minute
STANDARD_DEVIATION 5.2 • n=93 Participants
|
24.5 breaths/minute
STANDARD_DEVIATION 6.4 • n=4 Participants
|
24.2 breaths/minute
STANDARD_DEVIATION 5.8 • n=27 Participants
|
|
Glasgow Coma Scale.(GCS)
|
15 units on a scale
STANDARD_DEVIATION 0 • n=93 Participants
|
15 units on a scale
STANDARD_DEVIATION 0 • n=4 Participants
|
15 units on a scale
STANDARD_DEVIATION 0 • n=27 Participants
|
|
Hemoglobin (Hb)
|
7.6 g/dl
STANDARD_DEVIATION 1.4 • n=93 Participants
|
8.3 g/dl
STANDARD_DEVIATION 5.3 • n=4 Participants
|
8 g/dl
STANDARD_DEVIATION 3.4 • n=27 Participants
|
|
site of pain
Extremity
|
60 participants
n=93 Participants
|
58 participants
n=4 Participants
|
118 participants
n=27 Participants
|
|
site of pain
back
|
18 participants
n=93 Participants
|
27 participants
n=4 Participants
|
45 participants
n=27 Participants
|
|
site of pain
chest
|
30 participants
n=93 Participants
|
23 participants
n=4 Participants
|
53 participants
n=27 Participants
|
|
site of pain
others
|
12 participants
n=93 Participants
|
12 participants
n=4 Participants
|
24 participants
n=27 Participants
|
|
status
discharged
|
109 participants
n=93 Participants
|
108 participants
n=4 Participants
|
217 participants
n=27 Participants
|
|
status
Admitted
|
11 participants
n=93 Participants
|
12 participants
n=4 Participants
|
23 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 5, 10, 20,25,30, 40,45,50 60, 80, 100, 120 minutes post drug adminstrationPopulation: 3 patients in ketamine arm withdrew consent after 20 minutes in to the study while 1 patient in morphine arm was discontinued due to urticarial for fear of a worsened reaction if reexposed to the drug as he required a second dose
Our primary outcome measurement was the maximum change on the verbal NRS pain scale compared with their initial score (baseline). The NRS was used to measure a patient's subjective level of pain on a scale from 0 (representing no pain at all) to 10 (the worst pain imaginable) using whole numbers. The NRS score was documented just prior to the administration of the study drug (time zero). After infusion of the study drug was complete, NRS scores were documented at 5, 10, 20, and then every 20 minutes thereafter up to 120 minutes. We stopped recording NRS scores prior to 120 minutes if the patient requested a third dose of the study drug, withdrew consent or developed a severe adverse effect.
Outcome measures
| Measure |
Low Dose Ketamine
n=117 Participants
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=119 Participants
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Overall
|
-66.4 percent change from baseline NRS score.
Standard Deviation 29.9
|
-61.3 percent change from baseline NRS score.
Standard Deviation 28.7
|
|
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Excluding Treatment failures
|
-81.1 percent change from baseline NRS score.
Standard Deviation 18.0
|
-79.8 percent change from baseline NRS score.
Standard Deviation 16.9
|
|
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Among Treatment failures
|
-33.8 percent change from baseline NRS score.
Standard Deviation 24.2
|
-33.9 percent change from baseline NRS score.
Standard Deviation 19.1
|
|
Maximal Change in NRS Pain Scores as a Percentage of Baseline NRS Pain Score.
Those still at maximal effect at 120
|
-80 percent change from baseline NRS score.
Standard Deviation 18.7
|
-81.7 percent change from baseline NRS score.
Standard Deviation 17.0
|
SECONDARY outcome
Timeframe: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administrationFollowing dosage with study medication, the amount of time taken to demonstrate the maximal change in the patient's NRS pain score. Maximal change in NRS pain score is to be defined as the largest change from patient's baseline pain score. Duration of maximal change is how long the patient's pain score remained at this level.
Outcome measures
| Measure |
Low Dose Ketamine
n=120 Participants
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=120 Participants
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Time to Maximal Analgesic Effect and Duration of Action of Ketamine
time to maximal effect
|
19.8 minutes
Standard Deviation 14.4
|
34.1 minutes
Standard Deviation 22.1
|
|
Time to Maximal Analgesic Effect and Duration of Action of Ketamine
duration of maximal effect
|
60 minutes
Standard Deviation 28.7
|
58.5 minutes
Standard Deviation 30.3
|
SECONDARY outcome
Timeframe: 5, 10, 20, 40, 60, 80, 100, 120 minutes post drug administrationThe patient will be assessed for vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation), Ramsay Sedation Scale (RSS) score at 5,10,20 minutes following medication administration and then every 20 minutes until a total of 120 minutes from the first dose of study medication. outlying vital signs recorded.( systolic Blood pressure less than 90mmHg or greater than 150mmHg, Heart rate less than 50bpm or greater than 150bpm, oxygen saturation below 90%, respiratory rate below 9breaths/minute or greater than 40breaths/minute and RSS of 1 or greater than 3) The RSS was used to asses the level of agitation or sedation caused by the intervention .the scale ranges from 1(anxious/agitated) to 6( no response to stimulus-deep sedation) with 2 being the optimal (cooperative, oriented and tranquil).A checklist for side effects like airway problems, allergic reactions, salivation, dysphoria,nystagmus, respiratory/cardiac arrest, awakening hallucinations, nausea/vomiting was used
Outcome measures
| Measure |
Low Dose Ketamine
n=120 Participants
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=120 Participants
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Incidence of Side Effects, Including Outlying Vital Signs
|
45 participants
|
4 participants
|
SECONDARY outcome
Timeframe: 120 minutesRequiring more than two doses of the study medication provided for adequate pain control
Outcome measures
| Measure |
Low Dose Ketamine
n=120 Participants
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=120 Participants
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Incidence of Treatment Failure by Treatment Group.
|
34 participants
|
48 participants
|
Adverse Events
Low Dose Ketamine
Morphine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Dose Ketamine
n=120 participants at risk
Low dose ketamine 1mg/kg given as an IV infusion via syringe pump over 10 minutes. Maximum of 2 doses to be given during study period that will last 2 hours.
Low dose ketamine: Children in this arm shall receive a slow infusion of ketamine at a sub-anesthetic dose and monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
Morphine
n=120 participants at risk
Morphine 0.1mg/kg given as an IV infusion via a syringe pump over 10 minutes. Maximum of 2 doses to be given during the study period that will last 2 hours.
Morphine: Children in this arm shall receive intravenous infusion of morphine at analgesic dose and then monitored for pain, vital signs and side effects for 2 hours. Records will be taken at 5, 10, 20, 40, 60, 80, 100 and 120min.
|
|---|---|---|
|
Eye disorders
nystagmus
|
15.0%
18/120 • Number of events 18 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
Nervous system disorders
dysphoria
|
11.7%
14/120 • Number of events 14 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
General disorders
dizziness
|
3.3%
4/120 • Number of events 4 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.83%
1/120 • Number of events 1 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
Skin and subcutaneous tissue disorders
urticaric rash
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.83%
1/120 • Number of events 1 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
Skin and subcutaneous tissue disorders
pruritis
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
2.5%
3/120 • Number of events 3 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
Gastrointestinal disorders
Nausea & Vomiting
|
2.5%
3/120 • Number of events 3 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
|
Gastrointestinal disorders
over salivation
|
5.0%
6/120 • Number of events 6 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
0.00%
0/120 • 5, 10, 20,25, 30, 40,45,50,60,80,100, 120 minutes post infusion
|
Additional Information
Dr.Lubega Felix Anthony
Makerere University ,College of Health Sciences, Department of Anesthesia and Critical care
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place