Efficacy of Elixirium Thymi Compositum in the Treatment of Acute Bronchitis in Pediatric Patients

Official title

Assessing the Efficacy of Elixirium Thymi Compositum in the Treatment of Acute Bronchitis in Pediatric Patients (EXOTIC): A Double-blind, Randomized, Placebo-controlled, Phase 4 Study

Overview

The aim of this study is to evaluate the efficacy and safety of Elixirium thymi compositum (Formulae Normales (FoNo) VIII.) compared to a placebo in children between 6 and 17 years old to treat their acute bronchitis. The main question it aims to answer is: Is Elixirium thymi compositum (FoNo VIII.) safe and effective in the treatment of acute bronchitis compared to placebo?

Detailed description

Acute bronchitis is a common disease caused mainly by viral infections. Although there is a standard symptomatic therapy for it, antibiotics are often prescribed, which contributes to an increase in antibiotic resistance. Elixirium thymi compositum (FoNo VIII.) might be an alternative therapeutic option.

The aim is to establish the role of this product by evaluating its clinical efficacy and safety, meanwhile reducing the misuse of antibiotics in treating this condition.

This is a randomized, controlled, double-blinded, two-arm multicenter phase 4 trial. Eligible patients will be pediatric individuals between 6 and 17 years old diagnosed with acute bronchitis. The trial will enroll at least 56 eligible participants with a Total Bronchitis Severity Score (BSS) ranging from 5 to 12 points. Participants will be assigned randomly in a 1:1 ratio to receive either Elixirium thymi compositum at an age-dependent dosage (18-30 ml daily) for 5 days or a placebo with the same concentration and duration.

The trial's primary endpoint is the assessment of symptom improvement in acute bronchitis, as indicated by changes in the BSS score on Day 7. Secondary endpoints include evaluating use of concomitant medications and dietary supplements, safety and tolerability through reported adverse events, and the necessity of antibiotic usage. These secondary endpoints will provide deeper insights into the differences between the treatment and placebo groups. The primary and secondary endpoints will be monitored throughout a follow-up period of 7 days.

Interventions

• Combination product Elixirium thymi compositum (FoNo VIII.)
  During the study, the dosage is for children and adolescents as follows: 6 ml three times a day for 6-9 years, 8 ml three times a day for 9-15 years, and 10 ml three times a day for 15-17 years.
• Combination product Elixirium thymi compositum (FoNo VIII.) placebo
  During the study, the dosage is for children and adolescents as follows: 6 ml three times a day for 6-9 years, 8 ml three times a day for 9-15 years, and 10 ml three times a day for 15-17 years.

Primary outcome measures

• Bronchitis Severity Score [Time frame: From enrollment to the end of study at 7 days, measured on Day 0, Day 3 and Day 7.]

Secondary outcome measures (2)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: From enrollment to the end of study at 7 days.]
• Quality of life in acute bronchitis [Time frame: From enrollment to the end of study at 7 days.]

Eligibility criteria

Inclusion criteria

• age 6-17 years,
• diagnosis of acute bronchitis and the Total Bronchitis Severity Score of the patient is between 5-12 points,
• informed consent form and patient information leaflet signed by the patient and the parent or legal guardian, and
• no pregnancy, no planned pregnancy, and no breastfeeding.

Exclusion criteria

• allergy to the active ingredients or any other components of Elixirium thymi compositum,
• hypersensitivity to plants of the Lamiaceae family,
• chronic respiratory diseases such as asthma, chronic bronchitis, and chronic obstructive pulmonary disease,
• pneumonia in the last year,
• a history of recurrent or severe laryngotracheal stenosis due to inflammation,.
• active or chronic inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or infectious enterocolitis,
• heart failure (New York Heart Association Class II-IV),
• smoking (the patient currently smokes or has smoked at least one cigarette, cigar, or pipe daily),
• a diagnosis or history of lung cancer,
• a history of lung or chest surgery,
• epilepsy,
• any viral infection in the last 6-8 weeks,
• immunostimulant medications, antibiotics, or systemic steroid treatments in the past month,
• antihistamines, expectorants, or local steroids applied in the last two weeks,
• hereditary fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency,
• taking or planning to take hormonal contraceptives within the next 2 weeks
• chronic liver disease (e.g., cirrhosis) or acute hepatitis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Hungary · 1 center

• Noé Medical Center — Szeged

Publications

• Saust LT, Bjerrum L, Siersma V, Arpi M, Hansen MP. Quality assessment in general practice: diagnosis and antibiotic treatment of acute respiratory tract infections. Scand J Prim Health Care. 2018 Dec;36(4):372-379. doi: 10.1080/02813432.2018.1523996. Epub 2018 Oct 8. PMID 30296885
• Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):95S-103S. doi: 10.1378/chest.129.1_suppl.95S. PMID 16428698
• Cutrera R, Baraldi E, Indinnimeo L, Miraglia Del Giudice M, Piacentini G, Scaglione F, Ullmann N, Moschino L, Galdo F, Duse M. Management of acute respiratory diseases in the pediatric population: the role of oral corticosteroids. Ital J Pediatr. 2017 Mar 23;43(1):31. doi: 10.1186/s13052-017-0348-x. PMID 28335827
• Gonzales R, Sande MA. Uncomplicated acute bronchitis. Ann Intern Med. 2000 Dec 19;133(12):981-91. doi: 10.7326/0003-4819-133-12-200012190-00014. PMID 11119400
• Snyder RL, King LM, Hersh AL, Fleming-Dutra KE. Unnecessary antibiotic prescribing in pediatric ambulatory care visits for bronchitis and bronchiolitis in the United States, 2006-2015. Infect Control Hosp Epidemiol. 2021 May;42(5):612-615. doi: 10.1017/ice.2020.1231. Epub 2020 Oct 16. PMID 33059780
• Wenzel RP, Fowler AA 3rd. Clinical practice. Acute bronchitis. N Engl J Med. 2006 Nov 16;355(20):2125-30. doi: 10.1056/NEJMcp061493. No abstract available. PMID 17108344
• Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, Sande MA; Centers for Disease Control and Prevention. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann Emerg Med. 2001 Jun;37(6):720-7. doi: 10.1067/S0196-0644(01)70091-1. PMID 11385346
• Kowalczyk A, Przychodna M, Sopata S, Bodalska A, Fecka I. Thymol and Thyme Essential Oil-New Insights into Selected Therapeutic Applications. Molecules. 2020 Sep 9;25(18):4125. doi: 10.3390/molecules25184125. PMID 32917001

Identifiers

NCT: NCT07030855 · NNGYK/ETGY/03198-4/2025 · 2025-520845-61-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗