Efficacy of Intravenous Amboxol Hydrochloride as an Adjunct Therapy for Severe Pneumonia in Critically Ill Patients

This prospective, open-label, randomised controlled trial will be conducted in the Intensive Care Unit (ICU) of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). This study protocol will therefore be submitted for the approval of both the Research Committee of Anaesthesiology \& Intensive Care Unit, UKKMC and the Research \& Ethics Committee of UKMMC prior to its commencement. Written and informed consent will be obtained from the next of kin prior to the commencement of study by the medical doctors in charge of admitting the patients to ICU. These healthcare professionals will be receiving adequate training and information on IV ambroxol hydrochloride and the study protocol in the form of slideshow presentation. The data collection will be done by a single investigator. Intravenous preparation of ambroxol hydrochloride will be imported into Malaysia through customs following the procurement of Clinical Trial Import License.

METHODOLOGY

A total of 32 patients will be recruited based on the inclusion criteria. They will be randomised into either control group (Group C) or intervention group (Group A) using a computer-generated randomiser.

Group C will be receiving "standard therapy" for severe pneumonia as per recommended in the ICU Management Protocols by Malaysian Society of Intensive Care (MSIC). This includes antibiotics stewardship and supportive therapy. Group A will be receiving "standard therapy" as per control group with the addition of IV ambroxol 30mg TDS as adjunct therapy for 14 days. Each dose of 30mg of ambroxol will be diluted in 50ml of NS/D5% to be given intravenously over an hour. The patients will be considered as drop-outs if ambroxol is discontinued due to its side-effects, or if the patient's duration of ICU stay is less than 24 hours.

Data collection will begin from the day of ICU admission until the initial 14 days of ICU stay, until patient is extubated, or death, whichever occurs earlier. Demographic data including age, gender, weight, height, body mass index (BMI), concomitant Covid-19 status and co-morbidities will be documented. Co-morbidities that will be recorded include smoking status, obesity, diabetes mellitus, hypertension, cardiovascular disease, chronic lung disease, chronic kidney disease, malignancy and previous Covid-19 infection.

Clinical data such as ICU admission and discharge date, Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission, daily Sequential Organ Failure Assessment (SOFA) score, vasopressor requirements, renal replacement therapy during antibiotic therapy, date of intubation and extubation, reason for patient not being extubated by day 14, total duration of mechanical ventilation, incidence of reintubation within 48 hours and ICU outcomes (discharged alive or died in ICU) will also be recorded. The ICU scores used in this study will be used with permission from the publishers of APACHE II and SOFA scores.

Other clinical parameters that will be recorded daily include tracheal aspirate or sputum volume and character, body temperature, leukocyte count, and P/F ratio. Only one data representing the worst value such as highest temperature, lowest PF ratio will be recorded for each parameter daily. Chest X-ray and tracheal aspirate will be taken upon intubation, day 5 and day 10 of treatment. The C-reactive protein and serum procalcitonin level will be taken at less than 3 days and between 5 to 10 days of therapy. Any side effects will be recorded and managed accordingly.