Substance Withdrawal SyndromeSOWA-ICUNCT03435614

Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults

An observational study of Substance Withdrawal Syndrome, run by Marc M. Perreault at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Substance Withdrawal Syndrome
What is being tested?: Opioids
How many people: 29 participants
Where: 1 siteCanada
Study dates: 26 Feb 2018to 30 Sep 2018
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Mechanically ventilated adult ICU patients receiving continuous or regular intermittent opioids for more than 72 hours.

Who may be able to join

Patients requiring mechanical ventilation and receiving continuous or regular intermittent opioids for at least 72 hours.
Weaning of at least 10% from previous stable opioid dose. A weaning episode is defined as a ≥ 10% decrease in the total stable opioid dose received over 4 hours for opioid infusions and over 12 hours for intermittent opioid administration.

Who cannot join

Patient for whom consent cannot be obtained
Patient and/or family unable to communicate in French or English
Patient who is deaf without appropriate hearing aid
Imminent and predictable death (< 72 hours) according to medical team
Severe brain injury, defined as Glasgow Coma Scale (GCS) score of 8 or less at ICU admission
Moderate brain injury, defined as GCS between 9 and 12, with elevated intracranial pressure (ICP > 20 mmHg) which requires ICP monitoring and osmotherapy

Show all 13Show fewer

Acute neurological condition (e.g. status epilepticus, encephalopathy, stroke). If the acute neurological condition resolves within 72 hours, the patient may be included in the study.
Substance abuse prior to ICU admission.
Chronic alcohol use defined as alcohol consumption of more than 2 drinks/day and/or more than 14 drinks/week for men and 9 drinks/week for women.
Chronic use of illicit drugs and amphetamines (except amphetamines taken for therapeutic purposes) defined as a consumption of at least 3 times per week.
Chronic use of opioids (e.g. transdermal fentanyl, methadone, hydromorphone, etc.) defined as a consumption of at least 3 times per week.
Readmission to the MGH or RVH ICU during the recruitment period (limit of one study entry per patient)
Spinal cord injury above the lumbar region

Trial locations and contacts

1 site in 1 country.

Canada1 site

McGill University Health Centre
Montreal, Quebec, H4A3J1

Other trials in Canada

About this study

Mechanically ventilated critically ill adults may require prolonged administration of opioids to facilitate ventilator support and maintain comfort. The prolonged use has been associated with withdrawal symptoms upon rapid weaning in critically ill patients, known as the opioid-associated withdrawal syndrome (OIWS). Such withdrawal symptoms are well described in the paediatric population, however there is a lack of information in the adult population. Currently there is no bedside tool to rapidly identify such patients. Recognition of withdrawal symptoms is the basis for the development of an assessment tool to identify patients with OIWS.

Read the detailed description

Objectives:

To identify specific signs and symptoms of OIWS in mechanically ventilated adult intensive care unit (ICU) patients receiving at least 72 hours of regular opioids at the Montreal General Hospital (MGH) and the Royal Victoria Hospital (RVH) from February to October 2018.
To determine if a change in serum cortisol is associated with the presence of OIWS.

Hypotheses:

Considering our first objective is purely descriptive, no hypothesis can be stated.
OIWS is associated with an increase in serum cortisol.

Methods:

A prospective multicentre observational study will be carried out in two university-affiliated hospital ICUs (Montreal General Hospital and Royal Victoria Hospital). All mechanically ventilated adult ICU patients receiving regular (continuous or intermittent) opioids for more than 72 hours will be prospectively screened daily for withdrawal symptoms once the opioid dose is reduced by 10% or more. From that moment, daily evaluation by a physician using the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for opioid withdrawal will be conducted. Concomitantly, signs and symptoms of withdrawal will be collected by an investigator blinded to the DSM-5 assessment. These assessments will continue daily until the patient is transferred out of ICU or a maximum of 14 days and will be repeated once more between day 1 and day 4 post-transfer out of ICU.

A serum cortisol will be drawn on the first day of dose reduction by 10% or more (baseline) and will be repeated either after 72 hours or upon patient discharge from the ICU, whichever one occurs first.

Conditions: Substance Withdrawal Syndrome
Being tested: Opioids
Keywords: Opioid, Withdrawal, Critically ill adults, Cortisol
Medical subject headings: Substance Withdrawal Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OpioidsDrug
Also called Analgesics, Narcotics
Once an opioid dose reduction of 10% or greater is achieved, a daily assessment will be conducted by a physician using the DSM-5 criteria for opioid withdrawal. In addition, signs and symptoms of withdrawal will be collected daily by a blinded investigator.

Study groups in NCT03435614
Study group	Role	What they receive
Critically ill patients		Mechanically ventilated critically ill adults receiving regular opioids for more than 72 hours will be prospectively followed for the emergence of withdrawal symptoms upon weaning of opioids. Receives: Drug: Opioids

What is being measured

The primary outcome is the main question the study is designed to answer.

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
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.
Measured: 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

Secondary outcomes (1)

Change in Serum Cortisol Level
Cortisol level were drawn on the first day of opioid weaning and repeated 72 hours after onset of weaning
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 201830 Sep 2018

First posted19 Feb 2018
Study start26 Feb 2018
Primary completion30 Sep 2018
Study completion30 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Substance Withdrawal SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03435614
Sponsor's protocol ID: 2018-4305
Acronym: SOWA-ICU
Status last verified: Dec 2024
First submitted: 9 Feb 2018
Last updated: 1 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Chiu AW, Contreras S, Mehta S, Korman J, Perreault MM, Williamson DR, Burry LD. Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management. Ann Pharmacother. 2017 Dec;51(12):1099-1111. doi: 10.1177/1060028017724538. Epub 2017 Aug 9.
PubMed 28793780
Wang PP, Huang E, Feng X, Bray CA, Perreault MM, Rico P, Bellemare P, Murgoi P, Gelinas C, Lecavalier A, Jayaraman D, Frenette AJ, Williamson D. Opioid-associated iatrogenic withdrawal in critically ill adult patients: a multicenter prospective observational study. Ann Intensive Care. 2017 Sep 2;7(1):88. doi: 10.1186/s13613-017-0310-5.
PubMed 28866754
Cammarano WB, Pittet JF, Weitz S, Schlobohm RM, Marks JD. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med. 1998 Apr;26(4):676-84. doi: 10.1097/00003246-199804000-00015.
PubMed 9559604

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Substance Withdrawal Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Signs and Symptoms of Opioid-associated Iatrogenic Withdrawal in Critically Ill Adults
ClinicalTrials.gov ID: NCT03435614
Acronym / sponsor ID: SOWA-ICU / 2018-4305
Conditions: Substance Withdrawal Syndrome
Keywords: Opioid, Withdrawal, Critically ill adults, Cortisol
Study type: Observational
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Marc M. PerreaultUniversity, hospital or other
Study start: 26 Feb 2018 (actual)
Primary completion: 30 Sep 2018 (actual)
Study completion: 30 Sep 2018 (actual)
First posted: 19 Feb 2018 (actual)
Results: Posted 28 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Objectives:

To identify specific signs and symptoms of OIWS in mechanically ventilated adult intensive care unit (ICU) patients receiving at least 72 hours of regular opioids at the Montreal General Hospital (MGH) and the Royal Victoria Hospital (RVH) from February to October 2018.
To determine if a change in serum cortisol is associated with the presence of OIWS.

Hypotheses:

Considering our first objective is purely descriptive, no hypothesis can be stated.
OIWS is associated with an increase in serum cortisol.

Methods:

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Critically ill patients	–	Drug: OpioidsMechanically ventilated critically ill adults receiving regular opioids for more than 72 hours will be prospectively followed for the emergence of withdrawal symptoms upon weaning of opioids.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Mechanically ventilated adult ICU patients receiving continuous or regular intermittent opioids for more than 72 hours.

Key inclusion criteria (2 listed)

Patients requiring mechanical ventilation and receiving continuous or regular intermittent opioids for at least 72 hours.
Weaning of at least 10% from previous stable opioid dose. A weaning episode is defined as a ≥ 10% decrease in the total stable opioid dose received over 4 hours for opioid infusions and over 12 hours for intermittent opioid administration.

Key exclusion criteria (13 listed)

Patient for whom consent cannot be obtained
Patient and/or family unable to communicate in French or English
Patient who is deaf without appropriate hearing aid
Imminent and predictable death (< 72 hours) according to medical team
Severe brain injury, defined as Glasgow Coma Scale (GCS) score of 8 or less at ICU admission

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OpioidsAlso: Analgesics, NarcoticsOnce an opioid dose reduction of 10% or greater is achieved, a daily assessment will be conducted by a physician using the DSM-5 criteria for opioid withdrawal. In addition, signs and symptoms of withdrawal will be collected daily by a blinded investigator.	Drug	Critically ill patients

Primary outcome

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
Time frame: 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
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.

1 secondary outcome

Change in Serum Cortisol Level
Time frame: 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.

Results and safety

Results posted to the registry on 28 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Iatrogenic Withdrawal Syndrome (IWS) Positive	6	6
Iatrogenic Withdrawal Syndrome (IWS) Negative	23	23

Primary outcome: 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

Time frame: 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. Number. Unit: percentage of assessments

Measure	IWS Positive n = 6	IWS Negative n = 23
Restlessness (RASS = 1)	28.6	13.6
Agitation (RASS > 1)	28.6	4.9
Anxiety	57.1	30.6
Hallucinations	28.6	11.2
Insomnia/Sleep disturbance (< 4 hours of continuous sleep)	66.7	21.4
Mydriasis (pupil size > 2mm)	100	77.8
Systolic Blood Pressure (SBP) > 140 mmHg	85.7	53

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Symptom assessments were collected daily until transfer out of ICU, death or 14 days after start of patient remained in ICU; If patient was transferred, one additional data was collected up to 96 hours post-transfer out of ICU. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Critically Ill Patients	0 of 29 (0%)	0 of 29 (0%)	0 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28793780Chiu AW, Contreras S, Mehta S, Korman J, Perreault MM, Williamson DR, Burry LD. Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management. Ann Pharmacother. 2017 Dec;51(12):1099-1111. doi: 10.1177/1060028017724538. Epub 2017 Aug 9.
Background: PubMed 28866754Wang PP, Huang E, Feng X, Bray CA, Perreault MM, Rico P, Bellemare P, Murgoi P, Gelinas C, Lecavalier A, Jayaraman D, Frenette AJ, Williamson D. Opioid-associated iatrogenic withdrawal in critically ill adult patients: a multicenter prospective observational study. Ann Intensive Care. 2017 Sep 2;7(1):88. doi: 10.1186/s13613-017-0310-5.
Background: PubMed 9559604Cammarano WB, Pittet JF, Weitz S, Schlobohm RM, Marks JD. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med. 1998 Apr;26(4):676-84. doi: 10.1097/00003246-199804000-00015.
Individual participant dataSharing planned: No

Related trials for Substance Withdrawal Syndrome

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Marie-Soleil Delisle, MSc principal investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Marc M Perreault, PharmD principal investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Marc-Alexandre Duceppe, MSc principal investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Substance Withdrawal Syndrome, run by Marc M. Perreault at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03435614, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2025.