Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05663905 |
| Other study ID # |
JEP-2022-536 |
| Secondary ID |
FF-2022-376 |
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 7, 2023 |
| Est. completion date |
October 31, 2023 |
Study information
| Verified date |
December 2023 |
| Source |
National University of Malaysia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Ambroxol is a mucolytic containing an active N-desmethyl metabolite of bromhexine. It is
approved by both the U.S. FDA and EMA to be marketed under several formulations including
oral, nasal, oro-mucosal, rectal and intravenous formulations. One of ambroxol's authorized
use is for the treatment of bronchopulmonary infections. In addition, it has been found over
the decades to have other multi-pronged properties such as local anaesthesia,
anti-inflammatory and anti-oxidant effects. It also stimulates surfactant production in Type
II pneumocytes, thus preventing atelectasis in pneumonia. Ambroxol has demonstrated a wide
safety profile and is an extensively studied drug in terms of safety with the commonest side
effects being skin rashes, allergies, nausea, vomiting, abdominal pain and dyspepsia.
Severe pneumonia is is defined by the American Thoracic Society (ATS) as pneumonia that
requires ICU admission and specifically fulfils one of two major criteria, or three out of
nine minor criteria as per recommended in the latest ATS guideline.
This study aims to investigate the effects of using intravenous ambroxol as an adjunct
therapy on the resolution of severe pneumonia. The improvements in modified Clinical
Pulmonary Infection Score (CPIS) will be used as a surrogate for resolution of severe
pneumonia. Modified CPIS is a clinical score of 0-12 based on 6 clinical features: volume and
character of tracheal secretions, chest radiograph infiltrates, body temperature, leukocyte
count, oxygenation index, and microbiology results. Traditionally, CPIS score has been used
to facilitate the diagnosis of VAP where a cut-off point of >6 is used to denote possible
pneumonia. Interestingly, Luna et al has found that serial improvements in CPIS score can be
successfully used as a surrogate for pneumonia resolution with good correlation with eventual
survivability.
This study will also explore the effects of using ambroxol on other clinical outcomes of
patients with severe pneumonia, including ICU mortality, duration of ICU stay, length of
mechanical ventilation and incidence of reintubation within 48 hours. If this adjunct
treatment is able to reduce duration of ICU stay and length of MV, it will not only directly
impact the patients' short & long term outcomes but will also confer logistical benefits in
terms of saving resources and reducing healthcare economic burden while optimizing ICU
turnover rates.
Description:
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.
