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

NCT05663905 | Completed Phase 4 DMC

• 2 other identifiers: JEP-2022-536FF-2022-376
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Severe Pneumonia; Community-acquired Pneumonia; Hospital-acquired Pneumonia; Critical Illness

Keywords

mechanical ventilation; severe pneumonia; critical illness; CPIS; Ambroxol

Outcome Measures

Primary Outcomes (1)

• Rate of resolution of severe pneumonia

  Serial CPIS (Clinical Pulmonary Infection Score) will be used to compare rate of resolution of severe pneumonia between the 2 arms

  2 weeks

Secondary Outcomes (4)

• Duration of Mechanical Ventilation

  2 weeks

• Length of ICU Stay

  2 weeks

• Incidence of ICU mortality

  2 weeks

• Incidence of reintubation within 48 hours of extubation

  2 weeks

Study Arms (2)

Ambroxol Arm

EXPERIMENTAL

Amboxol arm will be receiving "standard therapy" as per control group with the addition of IV ambroxol hydrochloride 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.

Drug: Ambroxol Hydrochloride; Other: Standard Therapy

Control Arm

OTHER

Control arm will be receiving "standard therapy" for severe pneumonia as per recommended in the ICU Management Protocols by Malaysian Society of Intensive Care (MSIC).37 This includes antibiotics stewardship and supportive therapy.

Other: Standard Therapy

Interventions

Ambroxol Hydrochloride DRUG

IV ambroxol hydrochloride 30mg TDS as adjunct therapy to standard therapy for severe pneumonia in ICU for 14 days. Each dose of 30mg of ambroxol will be diluted in 50ml of NS/D5% to be given intravenously over an hour.

Also known as: Mucosolvan®, Lasolvan®

Ambroxol Arm

Standard Therapy OTHER

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.

Ambroxol Arm; Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged \> 18 years old
• Mechanically ventilated due to severe community or hospital acquired pneumonia

You may not qualify if:

• Patients aged \<18 years old
• Pregnant and lactating patients
• Patients with known allergies to ambroxol hydrochloride
• Patients with aspartate aminotransferase (AST) \>5 times the upper limit of normal at the time of recruitment
• Moribund patients who are expected to not survive within 24 hours of ICU admission

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

Hospital Canselor Tuanku Muhriz UKM (HCTM)

Cheras, Kuala Lumpur, 56000, Malaysia

Location

MeSH Terms

Conditions

Pneumonia; Community-Acquired Pneumonia; Healthcare-Associated Pneumonia; Critical Illness

Interventions

Ambroxol; Standard of Care

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bromhexine; Aniline Compounds; Amines; Organic Chemicals; Cyclohexylamines; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Associate Professor Dr. Aliza Mohamad Yusof, MD (UKM)

  Hospital Tuanku Muhriz UKM (HCTM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: December 23, 2022
• Study Start: January 7, 2023
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)