Clinical trial NCT03639558
Conditions: Psychiatric Emergency Aggression Agitation
Sponsor: Joseph Dib
Start date: 2018-08-28; Completion date: 2019-07-07
Enrollment: 100 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomised controlled trial comparing haloperidol + promethazine versus haloperidol + promethazine + chlorpromazine for agitated patients in the emergency department.

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.

Arms: arm 1: Haloperidol + Promethazine + Chlorpromazine are all psychiatric drugs that have been well tested. The combination of these 3 drugs, however, have never been randomised. arm 2: Haloperidol + Promethazine are both psychiatric drugs with antipsychotic and calming properties.
Interventions: intervention 1: Haloperidol + Promethazine + Chlorpromazine intervention 2: Haloperidol + Promethazine
Intervention descriptions: intervention 1: This is the usual treatment given by this hospital during an aggressive psychiatric episode. intervention 2: This is the second most used psycho-pharmacological combination used in this hospital during an aggressive psychiatric episode.

Protocol documents:
Prot_SAP_ICF_003.pdf: 
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Cover letter 
 
 
To whom it may concern, please find attached the protocol 
titled  ‘Protocol of a pragmatic randomised controlled 
trial of intramuscular haloperidol plus promethazine 
plus chlorpromazine versus intramuscular haloperidol 
plus promethazine plus chlorpromazine in the Lebanese 
psychiatric setting’ dated August 21, 2018 in PDF/A format.  
Kind regards,  
 


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Protocol of a pragmatic randomised controlled trial 
of intramuscular haloperidol plus promethazine 
plus chlorpromazine versus intramuscular 
haloperidol plus promethazine plus 
chlorpromazine in the Lebanese psychiatric 
setting. 
5.1 Overview 
Chapter IV was a systematic overview of relevant trials and it 
concluded with showing the emergency treatment used in 
Lebanon (See Chapter III) is unique to Lebanese medical 
practice. This chapter will focus on the trial protocol building 
on chapter III (treatment in Lebanese practice) and chapter IV 
(Systematic overview of relevant trials pertaining to rapid 
tranquilisation). 
This is a research protocol of the clinical trial that is to be 
conducted in the Lebanese psychiatry setting. It describes how 
the clinical trial will be conducted (I.e. objectives, statistical 
considerations, design, methodology and organisation) and 
ensures the ethical integrity of the trial subjects and data 
acquisition have been considered. Moreover, the protocol (now 
registered and published) serves as an indicator that the 
trialists will conduct the trial in accordance to what is 
presented in the trial protocol. Should the trial stray in any of 


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its aims (i.e. result objectives), the trialist is obliged to explain 
why changes were implemented.  
5.2 Introduction 
Aggressive and violence behaviour is a common behaviour 
seen in emergency psychiatric presentations with a prevalence 
of 3-10% (Tardiff & Koenigsberg, 1985). This aggression is 
due to a range of psychiatric disorders such as schizophrenia, 
bipolar disorder, substance use, and personality disorders as 
well as organic problems such as dementia although they are 
less frequent with the latter (Kaplan & Sadock, 1998). 
Guidelines recommend aggressive patients to be ‘verbally 
tranquilised’ in order for the attending physician to accurately 
and safely perform a diagnostic history and physical 
examination (The expert consensus guideline series, 1999). 
Since aggressive patients make this process difficult and 
potentially impossible, doctors and nurses face a dilemma and 
are required to work with limited evidence. Since the 
psychiatric team has a responsibility of ensuring the safety of 
everyone, rapid and safe tranquilisation becomes unavoidable. 
Medication and physical restraints are the available options 
when planning to calm and tranquilise an agitated patient. 
Medication can be given orally, intravenously (IV) or 
intramuscularly (IM). Oral and IV medications are usually not 


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possible when the patient is lashing out aggressively (Yildiz, 
Sachs, & Turgay, 2003). Depending on where in the world the 
management is happening, physical restraints may include 
straitjackets (Colaizzi, 2016), use of seclusion rooms (Crespi, 
1990) or medical restraints binding the patient safely to a bed 
using two or four points (Fisher, 1994; Saks, 1986). Physical 
restraining by staff is commonly employed.  
All options have advantages and disadvantages. For example, 
IV medication may work faster when tranquilising an agitated 
patient but may also lead to cardiac and respiratory problems 
– not to mention extreme difficulties implementing IV needles 
with an aggressive patient (Atakan & Davies, 1997). IM 
medications are easier to administer making them more 
efficient in terms of implementation. However, the time to 
onset of calming or sedation is longer and unpredictable 
compared to IV (Kaplan & Sadock, 1998). Physical restraints 
have the advantage of preventing patients from physically 
assaulting staff as well as causing self-injury. They also have 
the advantage of being more efficient when used in 
combination of drugs being delivered via IV or IM (Currier & 
Trenton, 2002). However, the disadvantages of restraints 
include out of date practice (depending on country) and time 
taken for patient to achieve a state of calm is profound when 
compared to pharmacological interventions (Miles & Irvine, 


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1992). It is imperative to find an evidence-base for a 
management scheme that is humane, socially acceptable and 
suited to tranquilise/calm aggressive patients safely and 
rapidly. This will help ensure the safety of both patients and 
the workers involved. TREC-Lebanon is a randomised, 
controlled, pragmatic and open study. Primary measure of 
outcome is tranquilisation at 20 minutes but effects on other 
measures of morbidity will also be assessed. TREC-Lebanon 
will involve the collaboration of many health care professionals 
– clinicians and psychiatric nurses in wards whereby the trial is 
taking place. Because the design of the trial does not 
substantially complicate clinical management, and in several 
aspects simplifies it, the study has the potential to be large 
and to evaluate treatments used in everyday practice. 
5.2.1 What is a randomised controlled trial?  
A randomised controlled trial is a type of study in which a 
number of similar people are randomly assigned to two (or 
more) groups in order to test a specific drug, treatment or 
intervention The experimental group receives the intervention 
being studied while the control group receives a placebo, no 
intervention or an alternate intervention. Outcomes are 
measured at specific times and the differences are examined 
statistically. This method is used to reduce bias (National 
Institute of Clinical Excellence, 2005). Figure 5.1 shown below 


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is a classic example of the basic structure of a randomised 
controlled trial (Akobeng, 2005). 
Figure 0.1: The basic structure of a randomised controlled trial 
 
5.2.3 What is a pragmatic randomised trial? 
The term explanatory is used to describe trials that aim to 
evaluate the efficacy of an intervention in a well-defined and 
controlled setting, Pragmatic or ‘real-world’, however, is used 
for trials designed to test the efficacy of the intervention in 
routine clinical practice (Patsopoulos, 2011). For example, a 
trial intended to inform a research decision regarding the 
benefit of a new drug is more likely to be explanatory 
reflecting ideal conditions while those for a later trial of the 
same drug intended to inform practical decisions by clinicians 
are more likely to be pragmatic as they reflect the usual 
conditions (Thorpe et al., 2009). The PRECIS instrument has 
been developed to guide trial design at the planning stage but 
also serves in other applications such as peer reviews attained 
in study reports (Winter & Colditz, 2014). 


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Figure 0.2: PRECIS tool  
5.2.4 
Rapid tranquillisation  
Rapid tranquillisation (RT) is not considered a ‘treatment’ for a 
persons’ mental health condition, but a short-term 
management technique for severely agitated and/ or 
aggressive behaviour in people experiencing psychotic 
distress. Due to its restrictive nature, RT should only be used 
as last resort when all other attempts to calm a situation via 
prevention (being environmentally aware and ensuring that 
adequate numbers of staff are present on ward) and de-
escalation (talking to and verbally trying to calm the person) 
has failed. These interventions should always be used in a way 
that respects human rights, and should never be used to 
manage patients as a substitute for adequate staffing 
(Department of Health, 2015).  


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5.2.5 Lebanese National Guidelines  
There are no Lebanese national guidelines pertaining to rapid 
tranquilization. As illustrated by Chapter IV, evidence from 
trials regarding the emergency intervention favoured in 
Lebanon (Chapter III – HPC) does not exist, although there is 
a good evidence base for the HP combination that is also used 
in Beirut. This affords opportunity to compare these two 
management plans, in real world circumstances, within a 
pragmatic randomised trial. This will be first of its kind 
comparing these two approaches, but also the first of its kind 
in psychiatry in Lebanon.   
5.2.6 TREC 
TREC-Lebanon derived its name from the first Brazilian TREC-
Rio study. TREC, in Portuguese, was an abbreviation for 
‘Tranquilização Rápida-Ensaio Clínico’ [Rapid Tranquilisation 
Clinical Trial]. TREC-Lebanon, similar to TREC-Rio and TREC-
India, will be investigating rapid tranquilisation within a clinical 
trial for treatment of agitated people in emergency psychiatric 
wards - in this case in Deir Salib – Lebanon’s largest and only 
public psychiatric hospital.  


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5.3 Methods 
5.3.1 Eligibility 
TREC-Lebanon is a pragmatic trial with wide, easily applied 
eligibility criteria that have been drawn up by the researcher 
(JD) working with partners in the Psychiatric Hospital of the 
Cross, Beirut.   
a. 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. 
1. Gender – both male and female 
2. Age (18-64)  
b. Exclusion criteria 
1. If the clinician KNOWS one treatment has benefit 
over another for a particular person 
2. If the clinician is aware of a contra-indication of one 
of the treatments 
3. If there is an Advanced Directive expressing a wish 
for one or other, or another treatment in the 
emergency setting  


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4. If the clinician does not want to undertake for both 
personal and professional reasons  
5. If the participant is known to be allergic to one or 
more of the interventions 
6. Already randomized 
7. Already sedated  
8. Accompanying person (Friend/Family/Police Officer) 
refuses patient trial entry. 
 
 


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Table 0.1: TREC- Lebanon plan 
Eligible if 
 
1. Patient is needing acute intramuscular sedation 
because of disturbed and dangerous behaviour 
2. Clinician is uncertain about the benefits and 
risks of haloperidol plus promethazine versus 
HPC 
Exclude if 
 
1. The Clinician believes that one 
treatment represents an additional risk 
for the patient 
Trial Entry 
 
2. Treatment is allocated using opening of 
consecutive TREC envelopes stored in 
the emergency drug cupboard. The 
envelope contains: 
1. The treatment paper slip indicating 
intervention to use 
2. TREC forms to be filled out by the 
attending doctor/resident 
3. TREC stickers for the patient’s notes 
Treatment 
 
4. Either: 
5. Haloperidol (2x5mg ampules) + 
promethazine (1x50mg ampules)  
Or: 
6. HPC (Haloperidol 5 mg, Promethazine 
50 mg and Chlorpromazine 100 mg 
ampule) 
7. One or other indicated on paper slip in 
the TREC envelopes 
8. All doses are at the discretion of the 
doctor 
Follow up 
 
1. All people for whom an envelope is 
opened will be followed up by the TREC 
study co-ordinators 
2. Data will be extracted from the notes on 
clinical state, hospital status, sedations, 
use of additional medications, and 
adverse reactions 
 
5.3.2 Interventions 
Placebo controlled studies in this area are difficult to justify on 
ethical grounds (see section on ethics in chapter Error! 
Reference source not found.) although the UK National 


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guideline (National Institute of Clinical Excellence, 2005) does 
use evidence from such studies (See here). TREC-Lebanon, 
however, will evaluate the existing care in the health services 
of Lebanon (Chapter VI) and this care involves the use of 
medication that is considered – and most likely is - both safe 
and effective. Currently, this protocol includes a comparison of 
an intramuscular haloperidol-promethazine mix (HP) with an 
intramuscular haloperidol-promethazine-chlorpromazine mix 
(HPC).  
The triple mix (HPC) is an obvious choice for TREC-Lebanon. It 
is perceived as effective, safe, and with adverse effects that 
are readily recognised by both medical and nursing staff in 
their routine care (See Chapter III). It is easy to administer by 
intra-muscular injection but has never been evaluated within a 
randomised control trial. As seen in Chapter III, the HP mix is 
also used in Beirut, albeit less frequently. Haloperidol, 
promethazine and chlorpromazine are on the WHO's Model List 
of Essential Drugs (See here) (World Health Organization, 
2015). 
a. Chlorpromazine 
Chlorpromazine is one of the three listed drugs for treating 
psychotic disorders in the World Health Organization's 
Essential Drug List (World Health Organization, 2013) (See 


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here). It is used across the globe for the 1% of people who 
suffer from this illness (de Haan & Liu, 2009). Chlorpromazine 
has a number of adverse effects, including a range of 
movement disorders (extrapyramidal symptoms) and 
anticholinergic and antihistaminic effects (Abidi & Bhaskara, 
2003). Chlorpromazine is known to be the most epileptogenic 
of the conventional antipsychotics causing seizures ranging 
from 1-4% depending on dosages (Hedges, Jeppson, & 
Whitehead, 2003).  
b. Haloperidol 
Haloperidol is an effective antipsychotic also listed in the World 
Health Organization’s Essential Drug List (World Health 
Organization, 2013)A key adverse effect caused by haloperidol 
are acute dystonias which are involuntary contractions of 
muscles all over the body such as the neck, face, pelvis, 
extremities, etc. and occur in 40% of all patients under 
haloperidol treatment (Kurz, Hummer, Oberbauer, & 
Fleischhacker, 1995b). They are not life threatening but can 
be distressing and frightening to the patient. Acute dystonias 
are successfully and swiftly treated with use of anticholinergic 
medication such as promethazine or procyclidine (Adams, 
Bergman, Irving, & Lawrie, 2013). However, these events are 
highly unpleasant and must further erode trust in the services.  


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c. Promethazine 
Promethazine hydrochloride is a first-generation H1 receptor 
antagonist, antihistamine, and antiemetic medication that can 
also have strong sedative effects ranging from mild to heavy 
and is used in relieving extrapyramidal symptoms caused by 
antipsychotic medications (Cantisani et al., 2013). 
Anticholinergic manifestations such as dry mouth, mydriasis, 
and blurred vision are usually present. Overdosage may also 
present with various cardiorespiratory symptoms such as 
respiratory depression, tachycardia, hypertension or 
hypotension, and extrasystoles (Lazarou, Pomeranz, & Corey, 
1998).  
d. The combinations 
It is well known that combining drugs can change - increase or 
decrease - the incidence of the known adverse effects 
(Lemmens, Brecher, & van Raelen, 1999) or result in novel 
effects unheard of with each drug on its own (Rummel-Kluge 
et al., 2010). The HP combination is, however, widely used 
and trusted. The addition of the promethazine to haloperidol 
may increase sedation, but decrease the acute dystonia so 
often seen with haloperidol alone. The latter was so common 
in the haloperidol alone arm of the TREC-Rio-II trial 
(Haloperidol vs. haloperidol + promethazine) and rare in the 


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second arm of that study that the trial was halted early by the 
Trial Steering Group (Huf, Coutinho, & Adams, 2007). It was 
felt that the combination treatment had considerable 
advantages over the haloperidol alone arm and that it was 
unethical to continue randomising to such a toxic treatment. 
(This latter treatment continues to be commonly employed 
within UK practice and can be seen in the 2017-2018 
Prescribing Observatory For Mental Health: Available to 
download here) (Prescribing Observatory for Mental Health 
(POMH-UK), 2018).  
The combination of haloperidol, promethazine and 
chlorpromazine (HPC) seems to be less commonly used than 
the combination of haloperidol and promethazine. However, 
HPC is still used in everyday practice at least Brazil and 
Lebanon (Dib et al., 2018a; Huf, Coutinho, & Adams, 2002). 
Whether the further addition of another drug (chlorpromazine) 
is a benefit or causes difficulties will, partly, be illustrated by 
the results of this study but no literature has been found to 
suggest that there are novel or even extreme adverse effects 
of this triple combination. Chapter III’s survey of Lebanon has 
shown that this intervention has been commonly used in 
psychiatric practice – probably for many years - with success 
in attaining rapid tranquilisation as well as causing very low 
incidence of adverse effects. 


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5.3.3 Setting 
The prevalence of serious mental illness across the world is 1-
2%. 80% of people live in low or middle income countries 
where typical antipsychotics such as haloperidol and 
chlorpromazine and/or benzodiazepines are readily available. 
Lebanon ranks as a low to middle income country (El Laithy, 
Abu-Ismail, & Hamdan, 2008). And, indeed, the ‘typical’ 
antipsychotics plus benzodiazepines are used (Chapter III).  
There are three mental hospitals and five psychiatric units 
within general hospitals in Lebanon. There are a total of 43 
psychiatric beds per 10,000 population (figure includes both 
psychiatric beds in general hospitals and mental hospitals). 
Two psychiatrists per 100,000 populations can be found in the 
general Lebanese population. Lebanon depends mainly on the 
private sector for the provision of the health services. The 
Ministry of Health has contracts with several private sector 
providers so patients can receive ‘free’ treatment. There are 
no disability benefits for persons with mental disorders and no 
disability funding for mental health (Berger, 2007). There are 
also no existing data on people who are treated in mental 
health hospitals, general hospital and community based 
psychiatric units. At best, by combining data from below on 
Lebanon’s economic social status and data from the WHO-
AIMS report on Mental Health in Lebanon (World Health 


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Organization, 2010), it can be assumed that since the majority 
of patients are treated in mental hospitals compared to 
community based psychiatric inpatient units (See Figure 5.3) 
and that the majority of the population require services from 
the Ministry of Health as they cannot afford private insurance, 
the majority of people seeking treatment for mental health 
would choose public psychiatric hospitals over private (Berger, 
2007). 
Figure 0.3: Patients treated in mental health facilities (rate per 
100.000 population) 
       
5.3.4 Size and statistical considerations 
Two main factors determine the number of people who should 
be recruited in a randomized trial in order for the trial to 
provide clear answers. They are the frequency of the 
investigated event and the size of the effect of treatment. It is 
important to avoid results that are erroneous. The probability 
of producing so called ‘false-positive’ results (Type I error – a) 
and ‘false negative’ findings (Type II error – B) is minimised 
by having adequate sample size. The aim of TREC-Lebanon is 


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to investigate whether people do ‘better’ if they get HPC or HP 
and ‘better’ – the primary outcome - is the proportion of 
patients’ calm/tranquil at 20 minutes.  
In such a stressful situation, even a small advantage for an 
intervention could represent a worthwhile benefit and so, 
TREC-Lebanon has been planned so that even a 15% 
difference in the proportion of tranquilised patients within the 
20 minutes could be detected. Realistically, and calculated 
from work in Chapter III and the time constraints of this PhD, 
TREC-Lebanon expects to involve a minimum of 90 patients 
across at least in a 3 month period.  
Table 0.2: Sample size needed to detect an absolute difference  
HP (% tranquilised) 
HPC 
(% 
tranquilised) 
N 
5 
20 
152 
10 
25 
200 
15 
30 
242 
20 
35 
276 
25 
40 
304 
30 
45 
326 
35 
50 
340 
 
As seen above sample size needed to detect an absolute 
difference of 15% in the proportion of tranquilised patients 
with alpha being 5% is greater than what TREC-Lebanon is 
projected to accrue. Therefore, TREC-Lebanon may well be 
underpowered to detect real effects and will not hold the same 
strength as TREC-Rio and TREC-India. However, the difference 


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between the two management strategies under test could be 
greater than 15%. Also, TREC-Lebanon is the first of its kind, 
it will serve as a vanguard for such studies in the Middle-East 
and properly test feasibility, as well as being a pilot for trials 
to come.  
5.3.5 Ethical and legal considerations 
The Helsinki Declaration (World Medical Association, 2013), 
the European Directive on Clinical Trials (European Parliament, 
2002) and the Nuffield Council documents on bioethics 
(Nuffield Council, 2000) state that trials in non-consenting 
patients are permitted on two conditions: i. no other context 
exists in which to answer the question; and ii. All trial 
participants get clear therapeutic benefit from whichever arm 
they are randomised to.  
The mental health system benefits from different acts and 
legislations in different areas of mental health (Berger, 2007), 
namely: 
1. Lebanese Act no. 72-9/9/1984 Welfare Act and 
Protection and Treatment of Mentally Ill Patients.  
2. Lebanese Act no. 673-16/3/1998 Narcotic Drugs and 
Psychotropic Substances and Precursors.  
3. Lebanese Act no. 220-29/5/2000 Rights of Mentally 
Handicapped in Lebanon.  


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4. Lebanese Act no 574-11/2/2004 Patients’ Rights and 
Informed Consent. 
Aggressive patients in a situation of psychiatric emergency are 
not able to give consent for their participation in a study. 
Drugs are usually given against the will of the patient. So, in 
the same way that doctors are responsible for the choice of a 
treatment in routine care, they take responsibility for the 
recruitment of a patient into the study as well as seeking 
consent. However, TREC-Lebanon will not involve 
administering an inactive compound to those who clearly need 
sedation/tranquillisation. Both treatments can calm the patient 
and there is no 'experimental' intervention. What is still 
uncertain is the speed for the onset of action, the duration of 
the effects and the different kinds of adverse reactions. TREC-
Lebanon will answer clinical questions to help the care of these 
people be more informed. TREC-Lebanon will also produce 
widely applicable findings, so that the treatment of people 
beyond Lebanon should also be safer.  
A patient/carer information leaflet about TREC-Lebanon is 
available for all for whom a TREC-Lebanon envelope is opened. 
Carers will always be free to decide that their relative should 
not be entered. Not being involved in TREC-Lebanon will not 
affect the person's standard of care. An information sheet is 


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provided detailing the aim and purpose of the study (See 5.8 
Appendix 1. TREC- Lebanon information for relatives). 
5.3.6 Randomisation  
Randomisation allows the distribution of the treatments in a 
way that is not a function of a clinical decision, but of pure 
chance. Clive Adams will undertake randomisation in the 
United Kingdom. Microsoft Excel 'RAND' function will be used 
to choose even numbered block sizes less than ten. Again 
using this function, the order of use of these block sizes will be 
randomised. Which drug regimen was represented by which 
number within the block was then selected, again at random. 
Tables of TREC-Envelopes numbered by contents will be 
constructed and will be supplied to a Lebanese colleague 
(Souheil Hallit). The tables will list the contents of the 
envelopes in groups of ten, not disclosing the block sizes used. 
The Lebanese colleague, always working independently of the 
TREC-Lebanon team, will ensure that the correct labels are in 
the TREC-envelopes before they are sealed. Concealment of 
allocation will be ensured by not disclosing the randomly 
varied block sizes to the colleagues packing the envelopes, the 
supply of tables to those colleagues that gives no suggestion 
that blocks are even being employed, the independence of 
those filling the envelopes from the other researchers or the 


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clinicians, and the identical nature of the sealed, fully opaque 
envelopes. 
These easy-to-use envelopes will be paper based, identical and 
consecutively numbered. The final check to ensure that 
nothing has gone wrong with the randomisation will be by the 
principal investigator (JD) filling in a form for each block of ten 
opened envelopes.  
5.3.7 TREC-Lebanon 
Because the TREC-Lebanon study evaluates care in the 
emergency situation, it is imperative that the doctors and 
nurses know which intervention is being given. The study is 
blind only up until the time that the TREC-Lebanon trial 
envelope is opened. Therefore, it is crucial that the evaluation 
of the severity of a person's disturbance and the first 
impression on the possible cause for the disturbed behaviour 
are recorded before the envelope is opened. Once the 
envelope is opened, doctors and nurses will have knowledge of 
the drug to be used. It is perfectly feasible that the knowledge 
that one drug has been given will influence the care beyond 
the actual effects of the medication. Keeping the study open is 
not only practical in the emergency situation, but also 
desirable as the evaluation of care being undertaken is as near 
real-world circumstances as is possible. 


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5.3.8 Protocol registration  
The objective of registering trial protocols is to establish a 
comprehensive register that would make all protocol of trials 
publicly available (Dickersin & Rennie, 2003). 
Reference number supplied by the chairman of the committee 
of The Psychiatric Hospital of the Cross Lebanon: HPC 
001/2018.  
Reference number supplied by the ethics board of the 
University of Nottingham: 271. 
5.4 Procedures 
All trial materials, and guidelines for their use, are to be 
provided in the TREC-Lebanon folder supplied by the co-
ordinating centre. What follows is a brief summary of all of 
trial procedures. 
5.4.1 Fitting into everyday practice  
The TREC-Lebanon trial is designed to not interfere with 
routine care. The process of randomisation is very similar to 
the normal procedure at the beginning of treatment and the 
eligibility criteria are simple. A paper slip indicating what 
intervention to use will be packed within the envelope. Data 
collection will be limited to the minimum necessary, and will 
involve little more than extraction of routine information by a 


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person designated to spend time on the TREC-Lebanon trial. It 
is not envisaged that busy doctors and nurses will be spending 
time filling out complicated forms. 
5.4.2 In the community 
Chapter III survey showed there are times when patients are 
brought in after having been given a sedative to calm down by 
their parents, friends or law officials. In this situation, as far as 
the clinician is concerned, he or she must still decide if the 
patient should be randomised if the patient is still exhibiting an 
agitated episode.  
5.4.3 Arrival at hospital 
Most people arrive at the hospital’s administrative centre are 
registered as a patient, and then transferred into their ward. If 
patients are presenting with violent conduct that could 
potentially harm people in their vicinity, they are taken 
immediately to the designated ward while those who brought 
them to the hospital (Family, friends, police officers, etc.) fill 
out paperwork and present their documents to the hospital’s 
administration. Patients that display an agitated episode 
requiring rapid tranquilisation are usually calm while waiting in 
the ward. Upon being told they cannot leave until they are 
feeling better, they may then display an agitation or 
aggression. 


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5.4.4 Triage to randomisation 
a. Eligibility and randomisation by envelope.  
Carers accompanying the disturbed person should have an 
opportunity to see the information leaflet (5.8 Appendix 1. 
TREC- Lebanon information leaflet for relatives) before 
randomisation. 
Anonymised information on participants who are not 
randomised / registered will include: 
• Age, 
• Gender, 
• Ethnicity (if applicable), 
The reason not eligible for trial participation, or if they are 
eligible but declined. 
Randomisation proceeds using a local pack system. Identical 
sealed treatment envelopes are provided. 
As soon as the person enters the study, the clinician completes 
the trial entry form on the top of the next consecutive 
envelope (See 5.9 Appendix 2. TREC-Envelope entry form – 
completed blind to treatment allocation). This must be 
completed before the treatment envelope is opened. It records 
brief baseline details about the person and the number of the 
treatment envelope. The treatment envelopes must be used in 


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order in which they are removed, the lowest number first. 
Once the trial entry form has been completed the person is in 
the trial, even if the doctor changes his/her management and 
the treatment envelope is not opened. 
 


August 18 2021 
TREC-PROTOCOL 
Procedures 
Page 27 
Table 0.3: Follow up enrolment 
Patient presenting with acute agitation or aggression. 
 
All measures taken to attempt to calm individual, including de-escalation measures, talking to the 
patient, consideration of placement, physical intervention (restraint) or seclusion. If these attempts to 
calm fail, and non-psychiatric causes for disturbed behaviour have been ruled-out, the patient will be 
immediately randomised to a rapid tranquillisation intervention. 
 
 
 
 
 
Not meeting Inclusion criteria 
 
 
 
 
Randomize 
 
 
 
 
 
 HP 
 
 
HPC 
 
 
 
 
 
[Consent sought from either participant (if capacity regained) or personal or 
professional legal representative as soon as practicable after the emergency has 
passed] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time to tranquillisation: calm/ lightly sedated. 
Over-sedation: asleep. 
Further RT doses are needed. 
Serious specific adverse effects and non-serious 
general adverse events. 
Need for restraint/ seclusion/ special nursing. 
By 20, 40, 60, 120 minutes after 
injection: 
 
 
 
 
 
 
 
 
Calm/ lightly sedated. 
Over-sedation: asleep. 
Adverse effects (any). 
Serious adverse effects. 
Additional tranquillising drugs. 
Need for restraint/ seclusion/ special nursing. 
Additional episodes of aggression/ agitation. 
Doctor called to see patient. 
Accepting oral medication 
By 24 hours after injection: 
 
 
 
 
 
 
 
 
 
No other episode of aggression. 
Doctor not called to see patient because of 
aggression. 
Accepting oral medication. 
Discharged. 
By 2 weeks after injection: 
 
 
 


August 18 2021 
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Procedures 
Page 28 
5.4.5 Participant Eligibility Criteria  
The eligibility criteria should be clear (See Eligibility above in 
Methods section).  
5.4.6 Trial envelopes  
As soon as the person has been found to be eligible, the next 
consecutive envelope is opened and a paper slip indicating 
what intervention to use is displayed. Each envelope contains: 
Paper slip indicating the use of haloperidol + promethazine 
(HP) 
1 × TREC-Lebanon follow-up form (Appendix 3, 
see Additional File 1) 
2 × TREC-Lebanon stickers for the drug prescription form 
and medical notes 
Or 
Paper slip indicating the use of haloperidol + promethazine 
+ chlorpromazine (HPC) 
1 × TREC-Lebanon follow-up forms (Appendix 3, see 
Additional File 1) 
2 × TREC-Lebanon stickers for the drug prescription form 
and medical notes 
All doses used are at the discretion of the attending clinician. 
If the contents of a trial envelope are destroyed, or unfit for 
use, the person should not be randomised a second time and 


August 18 2021 
TREC-PROTOCOL 
Procedures 
Page 29 
the equivalent material should be obtained from the research 
director (SH) if appropriate. 
In the event of continuing aggression despite the TREC-
Lebanon medication, on-going emergency management would 
be up to the discretion of the clinicians. Another envelope is 
not opened and the doctor is free to use any standard 
interventions. 
5.4.7 Outcome and follow-up 
It is crucial that follow-up is complete and accurate for 
everyone entered into the study. As a pragmatic study, 
causing minimal interference with routine care, TREC will not 
employ any rating scale outcomes. It is likely that completion 
of scales would be inaccurate, and incomplete, validity and 
reliability would be in question, and clinical utility problematic. 
The main outcome of TREC-Lebanon is tranquillisation by 20 
minutes. This primary outcome was requested by the nursing 
and medical staff of the hospital. By asking the relevant 
clinical staff to select the primary outcome for TREC-Lebanon 
we hoped to ensure maximum compliance with the trial 
protocol. Therefore, upon injection of the patient, a timer is 
started on the resident’s phone and this rings at 20 minutes 
and then again at 40, 60 and 120 minutes. At each period the 
attending resident rates whether the person is tranquil, 


August 18 2021 
TREC-PROTOCOL 
Procedures 
Page 30 
asleep, has shown adverse effects or needs additional 
treatment (see 5.9 Appendix 2. TREC-Envelope entry form - 
completed blind to treatment allocation). This attending 
resident is not blinded. The person is considered tranquillised 
when they are felt to be calm and peaceful, but not asleep. 
They should not be agitated or restless, nor displaying 
threatening verbal behaviour, physical aggression against 
objects, self-aggression or physical aggression to other 
people. Blinding this rater for every participant would have 
added additional complexity to the study that would have 
made the trial unacceptable to the emergency room staff. 
More importantly, it would have completely changed the 
emphasis of TREC-Lebanon. What is being evaluated is the 
real-world practice of giving two different drug regimens in the 
psychiatric emergency setting. In the real world situation 
health care professionals know what treatment is being given.  
In addition, nurse volunteers should they choose to participate 
can be an additional rater, blind to allocated treatment who 
will, unknown to the health professionals looking after the 
patient, time the period between injection and tranquillisation 
and / or sleep exactly. These data will be used to validate the 
rating of the follow up form (see 5.11 Appendix 4. Dr. 
Stopwatch Form). Additional data are then recorded at 24 


August 18 2021 
TREC-PROTOCOL 
Procedures 
Page 31 
hours and finally at two weeks (See 5.13 Appendix 6. TREC- 
Lebanon Main data collection form).  
All additional data are to be extracted from routine notes. If 
the person is transferred to another hospital, the co-ordinating 
centre will contact every hospital to find out further details on 
outcome after transfer. 
5.4.8 Data collection, entry and analysis 
All data for TREC-Lebanon will be collated from the TREC-
envelope forms and routine notes of each emergency room or 
ward (See 5.13 Appendix 6. TREC- Lebanon Main data 
collection form). These data, in compliance with the 
Nottingham ethics committee requests, will be protected via 
anonymising the personal data of trial participants. The data 
will be inputted onto Microsoft Access (Or a program of similar 
nature). 
Analysis will take place within this package and SPSS. Tables 
for this analysis are prepared before recruitment of the first 
patient (See 5.14 Appendix 7. Dummy Tables). All analysis will 
be based on groups as randomly allocated; this will be an 
intention-to-treat analysis. For the principal comparisons 
statistical significance will be taken at a 5% level, to minimise 
the impact of multiple comparisons. Relative risk, risk 
difference and 95% confidence intervals will be estimated for 


August 18 2021 
TREC-PROTOCOL 
Procedures 
Page 32 
tranquillisation by 20 (Primary outcome), 40 and 60 and 120 
minutes (Secondary to primary outcome). For simplicity, SPSS 
will primarily be used to run frequency tables. Revman will be 
used to calculate risk ratios and confidence intervals between 
interventions. 
5.5 Anticipated risks  
In the following subtopics I will discuss all the risk associated 
with the TREC-Lebanon along with how these will be assessed 
and mediated.  
5.5.1 Ineligible people entering the study 
It is possible though highly improbable that patients who do 
not fit the trial’s entry criteria may enter the study. Those that 
do will not be counted as part of the trial and their notes will 
be disregarded. Detecting ineligible patients will be seen in the 
data entry form left at the director of research’s office (SH) 
making it simple and direct to trace.   
5.5.2 Staff compliance with protocol 
Attending resident and nurse should monitor action of given 
intervention i.e. make sure given treatment has been injected 
properly. In the event that an agitated patient may break any 
of the treatment tools – mainly the syringe containing the 
treatment intervention or destroy the vial containing the 


August 18 2021 
TREC-PROTOCOL 
Anticipated risk 
Page 33 
intervention before being placed within the syringe, another 
TREC envelope should NOT be opened. Instead, attending 
resident should carry on as per hospital protocol and fill out 
the serious event form detailing the circumstances (See 
Appendix 5. Serious event form). Nurses should also detail the 
nature of compliance, as they would normally do in their 
notes. In the event a patient does break the syringe or 
capsule, the situation is rectified with the nurse bringing the 
emergency treatment as detailed in the paper slip in the 
envelope.  
5.5.3 Feasibility phase 
A feasibility phase will take place before the trial commences. 
The feasibility phase will include a limited number of envelopes 
(5) with contents known to the trialists. The feasibility phase is 
designed to test the trial’s procedure in practice in order to 
assess if any unforeseen circumstances arise. In the event 
such unforeseen circumstances do arise, the trialists will 
rectify and mediate in the most practical way possible. 
Changes will be noted by the head researcher (JD) and 
updated in the trial protocol. 
5.5.4 Additional envelopes 
Ineligible people entering the study (see above) are at risk of 
using trial envelopes designed for patients eligible for the trial 


August 18 2021 
TREC-PROTOCOL 
Anticipated risk 
Page 34 
only. This ultimately affects the balance of both intervention 
samples therefore one solution is that a limited number of 
TREC-Lebanon envelopes will be crafted or bought for the trial 
beforehand and will be placed in SH’s secure office to ensure 
the trial has a balanced sample between two groups. 
5.5.5 Toxicity and serious unexpected events 
After trial entry, clinical events are recorded, as usual, in the 
patients' notes. Complications and adverse events should be 
managed as usual. A serious unexpected event form (5.12 
Appendix 5. Serious event form) is provided, and will be sent 
to the TREC-Lebanon Co-ordinator (JD) as soon it is 
completed. As mentioned in the eligibility criteria above, the 
attending doctor retains the right to withdraw the patient and 
the Steering Committee evaluates the overall circumstances of 
the event. In the event toxicity levels are more prevalent than 
anticipated, the Steering Committee may terminate the trial. 
5.6 Trial organisation 
The TREC-Lebanon Co-ordinating Group: The co-ordinating 
centre of the Lebanese arm is based at the Institute of Mental 
Health University of Nottingham United Kingdom. The Co-
ordinating Group has overall responsibility for the design of 
the proposed trial and is responsible for all aspects of day to 
day trial administration. The Co-ordinating team is also 


August 18 2021 
TREC-PROTOCOL 
Trial Organization 
Page 35 
responsible for preparing reports for the steering committee. 
Membership: Joseph Dib, Clive E Adams, Souheil Hallit.  
5.6.1 Steering Committee  
The overall progress of the trial, adherence to protocol, patient 
safety and the consideration of new information will be 
monitored by a scientific and administrative Steering 
Committee. The membership of this committee is PS and RH.  
5.6.2 Data Monitoring Committee 
TREC-Lebanon will include a committee to oversee progress of 
the trial. Since TREC-Lebanon might take three to six months 
to complete, an independent data monitoring committee 
(DMC) will, in confidence, monitor results. This could be 
undertaken on a week to week or month to month basis 
depending on the collective agreement of all the members of 
the DMC. In the light of the interim data, and of any other 
evidence or advice they wish to seek, the DMC will inform the 
chair of the Steering Committee (PS) if, in their view: i. there 
is proof beyond reasonable doubt that for any particular group 
or subgroup treatment with one or other regiment is clearly 
indicated or contraindicated or: ii. it is evident that no clear 
outcome will be obtained. Proof beyond reasonable doubt may 
be taken as the difference of at least three standard deviations 
and at least one of the primary outcomes. 


August 18 2021 
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Trial Organization 
Page 36 
The DMC may communicate certain interim analysis to the SC 
or suggest certain protocol changes, but the Steering 
Committee will remain responsible for deciding which changes 
to adopt. The membership of this committee is: GA and JM. 
The committee will receive the first batch of data when trial 
participants are at a total of 50 along with information such as 
adverse effects, unforeseen circumstances and trial progress 
so far.  
5.6.3 Funding 
No participating centre will directly receive funds for 
involvement in TREC-Lebanon. By design, funding for the 
overall project is minimal. All funding is intramural and 
everyone involved is undertaking this project as part of their 
usual employment.  
5.6.4 Proposed policy for publication and authorship 
The success of the TREC-Lebanon trial depends on a collective 
collaboration of multiple people in different professions 
working in the hospital. As TREC-Lebanon trial is formulated as 
part of a PhD thesis program at the University of Nottingham, 
Joseph Dib is listed as primary author. However, due to the 
large number of people that may be involved in the study, 
general publication may not be able to name everybody that 
has contributed in minor ways to the study. Authorship will 


August 18 2021 
TREC-PROTOCOL 
Trial Organization 
Page 37 
depend on the substantial input onto the study. Every effort 
will be made to name everyone who has made such an effort 
within a collective authorship (the TREC-Lebanon Collaborative 
Group). The trial co-ordinator (JD) and research director of 
Deir Salib Hospital Souheil Hallit will meet to discuss principle 
authorships and potential journals of publication before final 
report is published.  
5.6.5 Access to data 
Once the study is completed, access to study and all its data 
will be anonymised and accessible as part of JD’s final thesis 
draft. All data is protected as per regulations of the Psychiatric 
Hospital of the Cross and Lebanese Law.  
5.7 Acknowledgments  
5.7.1 Thanks 
The authors acknowledge the work and efforts of the TREC-
Collaborative Group – some not listed as authors - to which 
this trial took permission, acceptance, study design and 
initiative in order to carry out TREC-Lebanon. 
The authors acknowledge the efforts of all employees at ‘Deir 
Salib Hospital’ Hôpital Psychiatrique De La Croix including all 
researchers, physicians, residents and nurses whose partaking 
in the trial made it possible.  


August 18 2021 
TREC-PROTOCOL 
Acknowledgements 
Page 38 
The author acknowledges all the efforts of the University of 
Nottingham and in the Institute of Mental Health facility where 
this study was planned and passed onto ethics for approval.  
5.7.2 Competing interests 
The research co-ordinator JD declares none.  
5.7.3 Prior beliefs 
Clive Adams did not foresee a noticeable difference between 
HP and HPC while Joseph Dib believed HPC would have greater 
benefits than HP.  


August 18 2021 
TREC-PROTOCOL 
 
Appendix 1. TREC-Lebanon information for relatives 
 
Page 39 
5.8 Appendix 1. TREC-Lebanon information for relatives 
5.8.1 Information Leaflet 
Dear Relative or Friend, 
RE: TREC study (Rapid Tranquilisation Clinical Trial). 
This hospital is taking part in the TREC study - helping to 
identify the very best treatment for agitated or aggressive 
people in an emergency situation. All drug treatments used in 
this hospital are safe, efficient, well established and familiar to 
the doctors and nurses. No one, anywhere in the world, knows 
which is the very best drug to use for the emergency situation 
in terms of speed of onset and recovery.  
Once it is clear that your friend/relative is so disturbed/unwell 
that medication is needed, and the doctor looking after their 
care thinks them to be eligible for the TREC study, they are 
given one of two short acting sedating drug treatments 
(haloperidol + promethazine or haloperidol + promethazine + 
chlorpromazine). The choice of the treatment is made in fair, 
random, way, as in a lottery.  
Participation in the study does not involve additional tests or 
examinations and everyone will receive the best care 
available. The TREC study has been approved by the Ethical 
Committee of Deir Salib Hospital. 


August 18 2021 
TREC-PROTOCOL 
 
Appendix 1. TREC-Lebanon information for relatives 
 
Page 40 
If you want additional information, get in touch with TREC 
Collaborator in this hospital (Dr Souheil Hallit).  
Thank you. 
Joseph Dib  
TREC Co-ordinator 
 
 


August 18 2021 
TREC-PROTOCOL 
 
Appendix 1. TREC-Lebanon information for relatives 
 
Page 41 
5.8.2 Consent form 
 
                        
                                      
PATIENT CONSENT FORM  
TREC-Lebanon 
Division of Psychiatry & Applied Psychology 
& 
Psychiatric Hospital of the Cross  
 
Dear friend, 
You have been allocated to TREC-Lebanon – a trial studying 
two of the hospital’s routine intervention drugs during 
emergency periods requiring rapid tranquilisation. While you 
were in a state of agitation, you were allocated to either a 
group receiving haloperidol + promethazine or haloperidol + 
promethazine +chlorpromazine. This trial is designed to see 
which, if any, of the groups work most efficiently. 
As your participation was involuntary, you may still change 
your mind about being involved. You are free to withdraw at 
any point post reading this form but not after data has been 
collected and anonymised as the trial co-ordinator will not 
know who you are. Withdrawal does not require a reason.   
What is the project about? 
 
The project is looking at rapid tranquilisation between two of 
the hospital’s routine interventions, and which works best.  
 


August 18 2021 
TREC-PROTOCOL 
 
Appendix 1. TREC-Lebanon information for relatives 
 
Page 42 
Who is being asked to take part, and why? 
 
Clinicians – that is doctors and nurses as they are part of the 
routine care treatment. 
Patients – that is patients exhibiting an aggressive episode 
requiring rapid tranquilisation.  
 
Has the research been of any personal benefit to me? 
 
Yes, either interventions you may have received are aimed at 
calming you down during a state of aggression.  
 
What will you do with the data? 
 
Once data has been collected, they will be anonymized by the 
lead researcher and inputted onto a transcription form 
whereby they will be analyzed in order to see differences 
between both intervention groups.   
 
If you have any questions or concerns, please don’t hesitate to 
ask.  
 
If you are interested in the results of the survey or if you wish 
to withdraw your data from TREC-Lebanon, please contact 
the head researcher (contact details below)  
 
THANK YOU FOR YOUR PARTICIPATION 
 
Head Researcher: Joseph Dib 
(joseph.dib@nottingham.ac.uk) 
Hospital Research Director: Dr. Souheil Hallit 
(souheilhallit@hotmail.com) 
 
 
If you have any queries or complaints about this study, please 
contact the head researcher at the first instance.  
 
If this does not resolve the query to your satisfaction, please 
write to the Administrator to the Division of Psychiatry & 
Applied Psychology’s Research Ethics Sub-Committee (MS-
DPAPEthics@nottingham.ac.uk, +44 (0)115 8232214) who will 
pass your query to the Chair of the Committee.  
 
This study has been ethically approved by both the University 
of Nottingham and the Psychiatric Hospital of the Cross.  


August 18 2021 
Chapter V 
 
Appendix 2. TREC-Envelope entry form-completed blind to treatment of allocation 
 
Page 43 
5.9 Appendix 2. TREC-Envelope entry form - completed blind to treatment of allocation 
5.9.1 TREC Entry Form 
Please answer the questions before you open the envelope, and leave the completed envelope in the 
TREC-Bin box 
TREC Number: 
 
 
Bulletin/Medical Notes  
number: 
 
 
 
 
 
 
Patient’s Name: 
 
 
 
 
 
 
How disturbed is this Person? 
 
Number (Choose only one option) 
 
1- Moderately 
2- Markedly 
 
 
3- Extremely 
4- One of the most disturbed 
people you have seen 
 
5- Other, Please describe 
 
 
 
 
 
 
 
 
 
 
In your opinion, which is the 
primary cause of this episode? 
 
Number (Choose only one option) 
 
 
1. Psychosis 
5. Other organic problem. Which 
one? 
2. Intoxication 
6. Psychological distress 
 
 
3. Dementia 
 
7. Unknown 
 
4. Mental retardation 
8. Other. Which one? 
 
 
 
 
 
 
Further details: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time of completing this form: 
 hh 
 mm 
 
 
 
 
 
 
 
Signature: 
 
 


August 18 2021 
Chapter V 
Appendix 3. Primary outcome 
Page 44 
5.10 Appendix 3. Primary outcome 
TREC number 
Medical no.  
Follow up Form 
Please take care completing this, Accuracy is important  
 
 
 
 
Have important adverse effects occurred?  
 Yes   
 No 
 
 
 
 
If 'Yes', please describe which occurred, and when. 
 
 
Please attach this to the prescription form. 
Thank you. 
 
Calm or 
tranquil? 
Asleep? 
Straitjacket +/-
Restraint? 
Important 
adverse effects? 
Left the 
ward? 
20 minutes after 
TREC medication  
 
 
 
 
 
40 minutes after 
TREC medication 
 
 
 
 
 
60 minutes after 
TREC medication 
 
 
 
 
 
2 hours after TREC 
medication 
 
 
 
 
 
TREC number 
Other comments 
Time of administration 
Hour 
 
Minutes 


August 18 2021 
Chapter V 
Appendix 4. Dr. Stopwatch form 
Page 45 
5.11 Appendix 4. Dr. Stopwatch Form 
Dr. Stopwatch form 
Time person was tranquilised  
 
Time person fell asleep 
 
 
When the person arrives in the Emergency Room 
observe the situation.  
When the person is given the TREC medication start 
the watch.  
Tranquilisation = 
when you feel the 
person is peaceful 
(whether asleep or 
not).  
 
Any other comments 


August 18 2021 
Chapter V 
Appendix 5. Serious event form 
Page 46 
TREC number 
5.12 Appendix 5. Serious event form 
Serious Event Form 
This form should be used to immediately notify the TREC Co-ordinator of any events that are serious 
and unexpected. 
Details of unexpected serious event – when started, when ended, management, outcome 
 
Patient’s name 
Name of responsible clinician 
 
Hospital name 
 
Bulletin or notes number 
Signature of person completing form 
Date form completed  
 
 
 
 
Please fax the 
completed form to the 
TREC Co-ordinating 
Centre.  
If fax is not possible, 
please communicate as 
soon as possible the 
local collaborator. 
Thank you 
 
 
Joseph Dib 
TREC Co-ordinator 
ADDRESS 
TEL: 
FAX: 
E-mail: 
msxjd6@nottingham.ac.uk 
 
 
 
 
 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 47 
5.13 Appendix 6. TREC-Lebanon Main data collection form 
Data transcription form 
Initial data 
Date of 
collection 
 
 
 
day  
month 
year 
Time of 
collection 
 
 
hour 
minutes 
TREC number 
 
ER / medical 
notes number 
 
Patient's name 
 
Sex 
 
M / F 
Date of birth 
 
 
 
or 
day  
month 
year 
Approximate 
age 
 
years 
 
Cause of 
agitation 
 
Transcribe the number 
on the TREC envelope 
Diagnosis
Severity of 
agitation 
 
Transcribe the number 
on the TREC envelope 
Date TREC 
envelope was 
opened 
day  
month 
year 
Time TREC 
envelope was 
opened 
 
 
hour 
minutes 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 48 
Name of person 
who opened the 
TREC envelope 
 
 
TREC drug(s)  
H+P / HPC 
Drug(s) given during the first 24 hours 
Name of 
drug 
Dose 
Route of 
administration* 
Time 
 
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 49 
hour minutes
 
 
 
 
 
hour minutes
* If oral, register only the time of first 
administration and the frequency that the drug 
was to be given, eg. Twice/day or four times/ day 
 
Were oral drugs refused 
in the first 24 hours? 
 
Yes / No / Not 
applicable (not 
perscribed oral 
medication) 
All these data should be on the prescription form. Is there 
anything you want to add? Please note it here. 
 
Emergency Drug(s) given during the first 24 hours 
Name of 
drug 
Dose 
Route of 
administration* 
Time 
 
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 50 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
 
 
 
 
 
hour minutes
* If oral, register only the time of first 
administration and the frequency that the drug 
was to be given, eg. Twice/day or four times/ day 
 
Were oral drugs refused 
in the first 24 hours? 
 
Yes / No / Not 
applicable (not 
prescribed oral 
medication) 
All these data should be on the prescription form. Is there 
anything you want to add? Please note it here. 
 
 
TREC Number 
 
First 
psychiatric 
attendance? 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 51 
Yes / No / 
Unknown 
Already on 
antipsychotics?  
Yes / No / 
Unknown 
Where did the 
patient go 
immediately 
after 
administration 
of TREC drugs?  
1-Transferred 
to ward  
2- Left the 
ward  
3- Transferred 
to another 
hospital 
4- Other 
In case of ‘Ward of 
another hospital’, 
which hospital? 
 
In case of ‘AWOL’, 
at what time did 
 
 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 52 
the patient go 
AWOL? 
Hour 
Minutes
In first the 24 
hours after the 
use of TREC 
drugs, was the 
doctor was 
called to see 
the patient?  
 
Yes / No / 
Unknown 
Have 
important 
adverse 
reactions been 
registered on 
the notes or 
chart within 
the first 24 
hours?  
 
Yes / No / 
Unknown 
If they have 
been 
registered… 
Type of 
reaction 
Approximate time 
 
 
 
hour 
minutes 
 
 
 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 53 
hour 
minutes 
 
 
 
hour 
minutes 
How were the adverse effects managed? 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 54 
All this information should be in the notes or ER chart. If there 
is anything you would like to add, please write it here. 
 
 
Which one? 
Do the notes 
record a diagnosis 
for this episode? 
 
Were there other 
episodes of 
aggressiveness in 
first the 24 hours? 
 
Yes / 
No 
If 
so…. 
 
 
 
 
day 
month 
hour minutes
Calm or Tranquil 
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 
Asleep  
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 
Straitjacket+/-  
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 55 
 
Any other 
comments
Restraint  
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 
Important adverse 
effects?  
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 
Left the ward? 
20 minutes/ 40 minutes/ 60 
minutes/ 2 hours 
Was the doctor 
called?  
Yes/ No/ Unknown 


August 18 2021 
Chapter V 
 
Appendix 6. TREC-Lebanon Main data collection form 
 
Page 56 
Please, staple this to the primary outcome form, and 
give it to Joseph Dib.  
Thank you. 


August 18 2021 
Chapter V 
Appendix 7. Dummy Tables 
Page 57 
5.14 Appendix 7. Dummy Tables 
5.14.1 Dummy table A. Characteristics of patients at trial 
entry 
 
Haloperidol + 
Promethazine 
(n = …) 
HPC 
(n = …) 
Mean age (SD) 
 
 
Sex 
Male 
Female 
 
 
First psychiatric attendance 
 Yes 
 No 
 Unknown 
 
 
*Severity of disturbance - first 
impression 
 moderately  
 markedly 
 severely  
 among the most extremely 
disturbed 
 
 
*Presumed cause for agitation 
 Psychosis (schizophrenia or 
mania) 
 Substance abuse 
 Mental organic (dementia or 
oligophrenia) 
 Clinical organic (metabolic, 
hormones, etc) 
 Psychological 
 Unknown 
 
 
* before opening the TREC envelope 
 
 


August 18 2021 
Chapter V 
Appendix 7. Dummy Tables 
Page 58 
5.14.2 Dummy table B. Compliance with the allocated 
treatment, and additional medication 
 
Haloperidol + 
Promethazine 
(n = …) 
HPC 
(n = 
…) 
Already on antipsychotics?  
 
 
Yes 
No 
 
 
Allocated treatment 
 
 
 
 
 
No allocated treatment 
 
 
Non-Emergency Drugs in the first 24 
hours (doses?) 
 
 
None 
 
 
Drug 
 
 
Drug 
 
 
Drug 
Drug 
Drug 
 
 
Emergency drugs in the first 24 hours 
(by class and route of administ) 
 
 
None 
 
 
Drug 
 
 
Drug 
Drug 
Drug 
 
 
Immediate placement 
 
 
Transferred to ward  
 
 
Left the ward 
 
 
Transferred to another hospital 
Other 
 
 
 


August 18 2021 
Chapter V 
Appendix 7. Dummy Tables 
Page 59 
5.14.3 Dummy table C. Primary measures of outcome  
 
 
Haloperidol + 
Promethazine 
 (n = …) 
HPC 
 (n = 
…) 
Tranquillisation 
% Tranquilised (Calm/Tranquil)  
By 20 minutes 
By 40 minutes 
By 60 minutes 
By 2 hours  
 
 


August 18 2021 
Chapter V 
Appendix 7. Dummy Tables 
Page 60 
5.14.4 Dummy table D. Secondary measures of outcome – first 24 hs 
 
 
Haloperidol + 
Promethazine 
 (n = …) 
HPC 
 (n = …) 
Tranquilisation (Calm or Tranquil after second agitated episode) 
 % tranquillised after 2 hours 
Sleep 
% asleep  
By 20 minutes 
By 40 minutes 
By 60 minutes 
By 2 hours 
 
 
Straitjacket +/- Restraint  
Indicate whether patient had straitjacket only or included restraint 
% needing physical restraints after TREC drugs 
 
 
 Mean time in physical restraints (SD) 
 
 
Revved Up Episode (Same agitated episode at different time 
Interval)  
By 20 minutes 
By 40 minutes 
By 60 minutes 
By 2 hours 
Second Agitated Episode (Agitated episode post 2 hours)  
Drugs used - by class and route of administration 
 
 
Adverse reactions 
 
 
 Acute dystonia 
 Mental confusion 
 Akathisia (motor restlessness) 
 Problems with vital signs 
 Other 
 
 
Immediate placement 
 
 
Transferred to ward  
 
 
Left the ward 
 
 
Transferred to another hospital 
Other 
 
 
Was the doctor called?  
 
 
Yes 
No 
Unknown  
 
 
 
 
 


August 18 2021 
Chapter V 
Appendix 7. Dummy Tables 
Page 61 
5.14.5 Dummy table E. Clinical progress / service outcomes / 
2 weeks 
 
Haloperidol + 
Promethazine 
(n = …) 
HPC 
(n = …) 
Diagnosis (If applicable)  
 
 
Diagnosis at 2 weeks or diagnosis 
at time of discharge, if that was 
before 2 week 
 
 
Length of stay – time to discharge 
 
 
% discharged 
by 1 week 
by 2 weeks 
 
 
 


August 18 2021 
Chapter V 
References 
Page 62 
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Chapter V 
Ethics forms 
Page 69 
5.16 Ethics Forms 
5.16.1 Lebanese document from chairman of the committee  
Figure 0.4: Lebanese ethics form 
 


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Figure 0.5: Liability waiver 
 


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Ethics forms 
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5.16.2 University of Nottingham ethics  
Figure 0.6: MTA questionaire 
 


August 18 2021 
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Page 72 
 
 
1.