Trial Outcomes & Findings for Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults (NCT NCT03435614)
NCT ID: NCT03435614
Last Updated: 2025-01-01
Results Overview
Percentage of daily assessments associated with each of the following signs and symptoms experienced by patients with and without OIWS (Restlessness (Richmond Agitation-Sedation scale = 1), Agitation (RASS \> 1), Anxiety, Hallucinations, Insomnia/sleep disturbance (\< 4 hours of continuous sleep), Mydriasis (Pupil diameter \> 2 mm) and systolic blood pressure (SBP) \> 140 mmHg. These assessments were performed once daily. Note that for the group of patients experiencing IWS, the data on signs and symptoms are limited to the assessment on the day that patients experienced OIWS. The signs and symptoms presented (Restlessness; Agitation; Anxiety, Hallucinations, Insomnia/sleep disturbance; mydriasis; SBP \> 140) were selected based on a \> 15 % absolute difference between both groups which was judged to be clinically significant.
COMPLETED
29 participants
From first day of opioid dose reduction until transfer out of Intensive care unit (ICU) or a maximum of 14 days, including one further assessment post-ICU transfer
2025-01-01
Participant Flow
Participant milestones
| Measure |
Iatrogenic Withdrawal Syndrome (IWS) Positive
Group of patients displaying signs and symptoms of IWS
|
Iatrogenic Withdrawal Syndrome (IWS) Negative
Group of patients not displaying signs and symptoms of IWS
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
23
|
|
Overall Study
COMPLETED
|
6
|
23
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults
Baseline characteristics by cohort
| Measure |
Opioid Iatrogenic WIthdrawal Syndrome (OIWS) Positive Patients
n=6 Participants
Mechanically ventilated critically ill adults receiving regular opioids for more than 72 hours whose at least one daily DSM-5 assessment for OIWS was positive following the reduction in opioid dose (opioid dose reduction of 10% or greater).
|
Opioid Iatrogenic Withdrawal Syndrome (OIWS) Negative Patients
n=23 Participants
Mechanically ventilated critically ill adults receiving regular opioids for more than 72 hours whose daily DSM-5 assessments for OIWS remained negative for the duration of follow up following the reduction in opioid dose (opioid dose reduction of 10% or greater).
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70 years
n=5 Participants
|
64 years
n=7 Participants
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
6 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
MIddle Eastern
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Serum Creatinine at ICU admission (umol/L)
|
124 umol/L
n=5 Participants
|
136 umol/L
n=7 Participants
|
132 umol/L
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
Diseases of the circulatory system
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
External causes of morbidity and mortality (trauma)
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
Infectious and parasitic diseases
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
Diseases of the digestive system
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
Diseases of the respiratory system
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Reason for ICU admission (ICD-10)
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Length of ICU stay
|
16.5 Days
n=5 Participants
|
16 Days
n=7 Participants
|
16.0 Days
n=5 Participants
|
|
Duration of mechanical ventilation
|
9.0 Days
n=5 Participants
|
9.0 Days
n=7 Participants
|
9.0 Days
n=5 Participants
|
|
Co-morbidities
Hypertension
|
3 participants
n=5 Participants
|
12 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Co-morbidities
Coronary artery disease
|
2 participants
n=5 Participants
|
11 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Co-morbidities
Diabetes
|
1 participants
n=5 Participants
|
8 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Co-morbidities
Chronic kidney disease
|
1 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Co-morbidities
Chronic obstructive pulmonary disease
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Co-morbidities
Other
|
3 participants
n=5 Participants
|
9 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
As needed use of opioids prior to ICU admission
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Use of benzodiazepines prior to ICU admission
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first day of opioid dose reduction until transfer out of Intensive care unit (ICU) or a maximum of 14 days, including one further assessment post-ICU transferPercentage of daily assessments associated with each of the following signs and symptoms experienced by patients with and without OIWS (Restlessness (Richmond Agitation-Sedation scale = 1), Agitation (RASS \> 1), Anxiety, Hallucinations, Insomnia/sleep disturbance (\< 4 hours of continuous sleep), Mydriasis (Pupil diameter \> 2 mm) and systolic blood pressure (SBP) \> 140 mmHg. These assessments were performed once daily. Note that for the group of patients experiencing IWS, the data on signs and symptoms are limited to the assessment on the day that patients experienced OIWS. The signs and symptoms presented (Restlessness; Agitation; Anxiety, Hallucinations, Insomnia/sleep disturbance; mydriasis; SBP \> 140) were selected based on a \> 15 % absolute difference between both groups which was judged to be clinically significant.
Outcome measures
| Measure |
IWS Positive
n=6 Participants
Group of patients with OIWS positive as per DSM-V criteria
|
IWS Negative
n=23 Participants
Group of patients without OIWS as per DSM-V criteria
|
|---|---|---|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Restlessness (RASS = 1)
|
28.6 percentage of assessments
|
13.6 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Agitation (RASS > 1)
|
28.6 percentage of assessments
|
4.9 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Anxiety
|
57.1 percentage of assessments
|
30.6 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Hallucinations
|
28.6 percentage of assessments
|
11.2 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Insomnia/Sleep disturbance (< 4 hours of continuous sleep)
|
66.7 percentage of assessments
|
21.4 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Mydriasis (pupil size > 2mm)
|
100 percentage of assessments
|
77.8 percentage of assessments
|
|
Description of Signs and Symptoms of OIWS in Patients Who Scored Positive for Withdrawal Syndrome (OIWS) According to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Criteria
Systolic Blood Pressure (SBP) > 140 mmHg
|
85.7 percentage of assessments
|
53 percentage of assessments
|
SECONDARY outcome
Timeframe: Baseline cortisol on first day of opioid dose reduction and on day 3 post-dose reduction, or on day of transfer out of ICU if patient is transferred before day 3.Population: Only 9 patients had two sets of blood samples drawn for cortisol levels measurement
Cortisol level were drawn on the first day of opioid weaning and repeated 72 hours after onset of weaning
Outcome measures
| Measure |
IWS Positive
n=1 Participants
Group of patients with OIWS positive as per DSM-V criteria
|
IWS Negative
n=8 Participants
Group of patients without OIWS as per DSM-V criteria
|
|---|---|---|
|
Change in Serum Cortisol Level
|
-146 nmol/L
|
-37 nmol/L
Interval -62.0 to 93.0
|
Adverse Events
Critically Ill Patients
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place