Study protocol for a randomised controlled trial of haloperidol plus promethazine plus chlorpromazine versus haloperidol plus promethazine for rapid tranquilisation for agitated psychiatric patients in the emergency setting (TREC-Lebanon)

Abstract

Background: Agitated and aggressive behaviours are common in the psychiatric setting and rapid tranquilisation is sometimes unavoidable. A survey of Lebanese practice has shown that an intramuscular haloperidol, promethazine and chlorpromazine combination is a preferred form of treatment but there are no randomised trials of this triple therapy. Methods: This is a pragmatic randomised trial. Setting - the psychiatric wards of the Psychiatric Hospital of the Cross, Jal Eddib, Lebanon. Participants - any adult patient in the hospital who displays an aggressive episode for whom rapid tranquilisation is unavoidable, who has not been randomised before, for whom there are no known contraindications. Randomisation – stratified (by ward) randomisation and concealed in closed opaque envelope by independent parties. Procedure – if the clinical situation arises requiring rapid tranquilisation, medical residents overseeing the patient will open a TREC-Lebanon envelope in which will be notification of which group of treatments should be preferred [Haloperidol + Promethazine + Chlorpromazine (HPC) or Haloperidol + Promethazine (HP)], along with forms for primary, secondary and serious adverse effects. Treatment is not given blindly. Outcome - primary outcome is calm or tranquil at 20 minutes post intervention. Secondary outcomes are calm/tranquil at 40, 60 and 120 minutes post intervention, asleep, adverse effects, use of straitjacket and leaving the ward. Follow-up will be up to two weeks post randomisation. Discussion: Findings from this study will compare the HPC versus HP combination used in Lebanon’s psychiatry emergency routine practice. Trial registration: ClinicalTrials.gov NCT03639558. Registration date, August 21, 2018.

Rapid tranquillisation in a psychiatric emergency hospital in Lebanon: TREC-Lebanon – a pragmatic randomised controlled trial of intramuscular haloperidol and promethazine v. intramuscular haloperidol, promethazine and chlorpromazine

“…Our survey predicted a 70:30 split for men and women but the trial is almost 50:50. We found no evidence of a selection bias at trial entry (Dib, 2020). We initially assumed that clinicians could have had a lower threshold of what constitutes an aggressive episode for women.…”

“…The remaining patients were brought in by friends or officers of the law (Dib et al, 2018). When relatives were present and the potential trial participant clearly lacked capacity (Dib et al, 2019), the clinician used a consent sheet and direct interview to inform relatives of the nature of the trial, its risks and benefits and their right to withdraw their relative for whatever reason without detriment to their care. If relatives were not present and the patient clearly lacked capacity yet needed treatment that could not be delayed, this patient was entered into the trial.…”

“…The Lebanon-UK team felt this to be an opportunity to undertake a pragmatic trial, designed in Beirut, of practice used locally and providing outcomes of relevant to routine practice. Post survey and after a process of local consultation, the protocol for TREC † 1 -Lebanon was developed (Dib et al, 2019) and registered (Clinical Trials.gov, 2018).…”