TREC-Lebanon: A Trial for Rapid Tranquilisation for Agitated Patients in the Emergency Setting

• Sponsor: Joseph Dib (Other)
• Overall Status: Completed
• CT.gov ID: NCT03639558
• Collaborator: University of Nottingham (Other), Hopital Psychiatrique De La Croix (Other)
• Enrollment: 100
• Locations: 2
• Arms: 2
• Actual Duration (Months): 10.3
• Patients Per Site: 50
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

This is a randomised controlled trial comparing haloperidol + promethazine versus haloperidol

• promethazine + chlorpromazine for agitated patients in the emergency department.

Condition or Disease	Intervention/Treatment	Phase
Psychiatric Emergency; Aggression; Agitation	Drug: Haloperidol + Promethazine + Chlorpromazine; Drug: Haloperidol + Promethazine	Phase 4

Detailed Description

This is a randomised controlled trial comparing haloperidol + promethazine versus haloperidol

• promethazine + chlorpromazine for agitated patients in the emergency department. Around 10% of patients will present to the psychiatric emergency unit with a violent episode that requires rapid tranquilisation. Surveys of practice and opinion has shown that variety of methods have been used and no universal option exists. This study will look at Haloperidol plus promethazine versus haloperidol plus promethazine plus chlorpromazine in violent aggressive psychiatric patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: TREC-Lebanon Trial: A Randomised Controlled Trial for Rapid Tranquilisation for Agitated Patients in the Emergency Setting
• Actual Study Start Date: Aug 28, 2018
• Actual Primary Completion Date: Jul 1, 2019
• Actual Study Completion Date: Jul 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Haloperidol + Promethazine + Chlorpromazine Haloperidol + Promethazine + Chlorpromazine are all psychiatric drugs that have been well tested. The combination of these 3 drugs, however, have never been randomised.	Drug: Haloperidol + Promethazine + Chlorpromazine; This is the usual treatment given by this hospital during an aggressive psychiatric episode.; Other Names: HPC
Experimental: Haloperidol + Promethazine Haloperidol + Promethazine are both psychiatric drugs with antipsychotic and calming properties.	Drug: Haloperidol + Promethazine; This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.; Other Names: HP

Outcome Measures

Primary Outcome Measures

1. Number of Participants According to the Time Taken for Aggressive Behaviour to Change to Calm and Tranquil [20, 40, 60 and 120 minutes post intervention treatment]

   Patient no longer exhibiting aggressive behavior both verbal and physical post intervention treatment. A primary measure of outcome form will contain a Calm or Tranquil column followed by four rows: 20 mins, 40 mins, 60 mins and 120 mins post intervention medication. The boxes would be ticked depending if the patient meets the primary measure of outcome within the time frame provided.

Secondary Outcome Measures

1. Time Taken for Patient to Fall Asleep Post Intervention [20, 40, 60 and 120 minutes post intervention treatment]

   Patient has fallen asleep and is no longer aggressive post intervention treatment and will be noted on the outcomes form which includes a checklist of different time intervals: 20, 40, 60 and 120 minutes post intervention treatment.

2. Time Patient Was Placed in Straitjacket/Restraint Post Intervention Treatment [20, 40, 60 and 120 minutes post intervention treatment]

   If patient was placed in a straitjacket post intervention due to aggression - this would be noted on the outcomes form which includes a checklist at certain time intervals 20,40,60 and 120 minutes post intervention treatment.

3. Time Noted Where Important Adverse Effects Occurred Post Intervention [20, 40, 60 and 120 minutes post intervention treatment]

   If patient exhibits any adverse effects post intervention treatment, this will be noted within the time frames.

4. Time Patient Left the Ward Against Medical Advice During the Time Period After the Intervention Was Administered. [20, 40, 60 and 120 minutes post intervention treatment]

   If patient had to leave ward against medical advice during intervention phase - the time will be noted as well as the reason to why patient left.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patient will be eligible if (1) requiring emergency acute intramuscular sedation because of disturbed and dangerous behaviour and (2) if the clinician is uncertain of the benefits between haloperidol plus promethazine vs haloperidol plus promethazine plus chlorpromazine.

• Gender - both male and female

• Age (18-64)

• Clinician is unaware on the effects of either treatment interventions

Exclusion Criteria:

• If the clinician KNOWS one treatment has benefit over another for a particular person

• If the clinician is aware of a contra-indication of one of the treatments

• If there is an Advanced Directive expressing a wish for one or other, or another treatment in the emergency setting.

• If the clinician does not want to undertake for both personal and professional reasons.

• If the participant is known to be allergic to one or more of the interventions

• Already randomized

• Already sedated

• Accompanying person (Friend/Family/Police Officer) refuses patient trial entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Psychiatrique De La Croix	Beirut	Jal L Dib	Lebanon
2	Psychiatric Hospital of the Cross	Beirut		Lebanon

Sponsors and Collaborators

• Joseph Dib
• University of Nottingham
• Hopital Psychiatrique De La Croix

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Aug 21, 2018

More Information

Publications

None provided.

• Responsible Party: Joseph Dib, Director of Trial Research, Hopital Psychiatrique De La Croix
• ClinicalTrials.gov Identifier: NCT03639558
• Other Study ID Numbers: DPAP - 2018 - 0138 - 1
• First Posted: Aug 21, 2018
• Last Update Posted: Jun 14, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Emergencies; Aggression; Promethazine; Diphenhydramine; Haloperidol; Chlorpromazine; Haloperidol decanoate

Study Results

Participant Flow

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Period Title: Overall Study
STARTED	52	48
COMPLETED	51	43
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine	Total
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.	Total of all reporting groups
Overall Participants	52	48	100
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	52 100%	48 100%	100 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37 (11.4)	36 (12.3)	36 (11.8)
Sex: Female, Male (Count of Participants)
Female	27 51.9%	22 45.8%	49 49%
Male	24 46.2%	21 43.8%	45 45%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	52 100%	48 100%	100 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants According to the Time Taken for Aggressive Behaviour to Change to Calm and Tranquil
Description	Patient no longer exhibiting aggressive behavior both verbal and physical post intervention treatment. A primary measure of outcome form will contain a Calm or Tranquil column followed by four rows: 20 mins, 40 mins, 60 mins and 120 mins post intervention medication. The boxes would be ticked depending if the patient meets the primary measure of outcome within the time frame provided.
Time Frame	20, 40, 60 and 120 minutes post intervention treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Measure Participants	52	48
Calm or tranquil at 20 minutes	18 34.6%	14 29.2%
Calm or tranquil at 40 minutes	41 78.8%	25 52.1%
Calm or tranquil at 60 minutes	45 86.5%	35 72.9%
Calm or tranquil at 120 minutes	47 90.4%	35 72.9%

2. Secondary Outcome

Title	Time Taken for Patient to Fall Asleep Post Intervention
Description	Patient has fallen asleep and is no longer aggressive post intervention treatment and will be noted on the outcomes form which includes a checklist of different time intervals: 20, 40, 60 and 120 minutes post intervention treatment.
Time Frame	20, 40, 60 and 120 minutes post intervention treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Measure Participants	52	48
Asleep at 20 minutes	0 0%	2 4.2%
Asleep at 40 minutes	9 17.3%	9 18.8%
Asleep at 60 minutes	25 48.1%	10 20.8%
Asleep at 120 minutes	24 46.2%	18 37.5%

3. Secondary Outcome

Title	Time Patient Was Placed in Straitjacket/Restraint Post Intervention Treatment
Description	If patient was placed in a straitjacket post intervention due to aggression - this would be noted on the outcomes form which includes a checklist at certain time intervals 20,40,60 and 120 minutes post intervention treatment.
Time Frame	20, 40, 60 and 120 minutes post intervention treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Measure Participants	52	48
Restraints at 20 minutes	17 32.7%	16 33.3%
Restraints at 40 minutes	10 19.2%	13 27.1%
Restraints at 60 minutes	8 15.4%	9 18.8%
Restraints at 120 minutes	6 11.5%	5 10.4%

4. Secondary Outcome

Title	Time Noted Where Important Adverse Effects Occurred Post Intervention
Description	If patient exhibits any adverse effects post intervention treatment, this will be noted within the time frames.
Time Frame	20, 40, 60 and 120 minutes post intervention treatment

Outcome Measure Data

Analysis Population Description

Total number of participants who were analysed for adverse effects post intervention. No patients exhibited adverse effects in this study.

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Measure Participants	52	48
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Time Patient Left the Ward Against Medical Advice During the Time Period After the Intervention Was Administered.
Description	If patient had to leave ward against medical advice during intervention phase - the time will be noted as well as the reason to why patient left.
Time Frame	20, 40, 60 and 120 minutes post intervention treatment

Outcome Measure Data

Analysis Population Description

Data not collected.

Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine	Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.	Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
Measure Participants	0	0

Adverse Events

Time Frame	10 months from time of intervention.
Adverse Event Reporting Description	No change of definitions pertaining to adverse events. No further relevant information to be provided.
Arm/Group Title	Haloperidol + Promethazine + Chlorpromazine		Haloperidol + Promethazine
Arm/Group Description	Haloperidol + Promethazine + Chlorpromazine: This is the usual treatment given by this hospital during an aggressive psychiatric episode.		Haloperidol + Promethazine: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.
All Cause Mortality
	Haloperidol + Promethazine + Chlorpromazine		Haloperidol + Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/48 (0%)
Serious Adverse Events
	Haloperidol + Promethazine + Chlorpromazine		Haloperidol + Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	Haloperidol + Promethazine + Chlorpromazine		Haloperidol + Promethazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0%)		0/48 (0%)

Limitations/Caveats

Possible limitations for this trial are that there are no Emergency Departments; therefore residents must always carry the TREC envelopes at all times, increasing the risk for error (i.e. misplacing envelope, using wrong envelope, etc.). Despite the limitation, the chances of error remain low due to the small sample size of 100.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.