CHAO Tos: Codeina, HederA Helix, LevOdropropizina Para la TOS (CHAO TOS)

A Double-Blind Randomized Clinical Trial Comparing Levodropropizine, Codeine, Ivy Leaf (Hedera Helix Extract), and Placebo for the Treatment of Acute Cough in Adults With Upper Respiratory Tract Infections in Primary Care

Upper respiratory tract infections affect millions globally, with cough being one of the most bothersome symptoms. While various treatments exist, their comparative effectiveness remains unclear. This study aims to evaluate and compare three commonly used treatments for acute cough in adults with upper respiratory tract infections: Levodropropizine, Codeine (with Pseudoephedrine and Chlorphenamine), and Ivy Leaf (Hedera Helix Extract). Investigators will conduct a double-blind, parallel-group randomized clinical trial with 184 adults aged 18-65 with acute upper respiratory tract infection and moderate to severe cough. Participants will be randomized to receive Levodropropizine, Codeine + Pseudoephedrine + Chlorphenamine, Ivy Leaf, or Placebo three times a day for 4 days. The primary outcome is cough severity at 48 hours, measured by a cough numerical rating scale. Secondary outcomes include cough severity and duration at 4- and 10-days. This trial will provide high-quality evidence comparing the efficacy of three widely used antitussive medications in primary care settings. The results could help establish evidence-based guidelines for treating acute cough in upper respiratory infections.

Study Overview

• Status: Completed
• Conditions: Upper Resp Tract Infection
• Intervention / Treatment: Drug: Levodropropizine; Drug: Codeine; Drug: Ivy Leaves Cough Liquid; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 4

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have between 18 and 65 years of age.
2. Have an URTI with Jackson Score ≥6 points.
3. Have moderate or severe cough assessed by having a score ≥2 points in the cough domain of the Jackson Score and ≥60mm on the cough visual analogue scale (VAS).
4. Have initiated cough within 5 days of enrollment.
5. Be capable of understanding and complying with study procedures.
6. Sign a written informed consent.

Exclusion Criteria:

1. Physician considers that potential participant needs or might need to use antibiotics at the screening visit (e.g., suspected bacterial otitis, bacterial tonsilitis, bacterial sinusitis, bacterial bronchitis, or bacterial pneumonia) or suspected need for antibiotics during patient follow-up.
2. Individuals with pre-existing respiratory conditions, including asthma, chronic obstructive pulmonary disease (COPD), or any chronic lower respiratory tract disease.
3. Uncontrolled cardiovascular condition (hypertension, diabetes, etc.)
4. Contraindications to use Levodropropizine, Codeine, Pseudoephedrine, Chlorphenamine, or Ivy Leaf (Hedera Helix Extract), including Fructose Intolerance, Bronchorrhea, Kartagener Syndrome, Ciliary Dyskinesia, Respiratory Failure, Bronchial Obstructive Syndrome, severe Hypertension, Peptic Ulcer, using Monoamine Oxidase Inhibitors (MAOIs), CYP2D6 ultra-fast metabolizers.
5. Pregnancy, suspected pregnancy, desired pregnancy, or breastfeeding.
6. Contraindications to the study medications will also result in exclusion, including known or suspected allergies to Levodropropizine, Codeine, Pseudoephedrine, Chlorphenamine, or Hedera Helix Extract.
7. Known adverse reactions to Levodropropizine, Codeine, Pseudoephedrine, Chlorphenamine, or Hedera Helix Extract.
8. Participants currently using medications that could interfere with study outcomes, such as other cough suppressants, inhalers, or systemic corticosteroids.
9. Researcher considers participant might not comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levodropropizine; Levodropropizine 30mg/5ml: 10ml three times per day during 4 days	Drug: Levodropropizine; Levodropropizine 30mg/5ml: 10ml three times per day during 4 days
Experimental: Codeine; Codeine 10mg/5ml + Pseudoephedrine 7.5mg/5ml + Chlorphenamine 0.5mg/5ml: 10ml three times per day during 4 days	Drug: Codeine; Codeine 10mg/5ml + Pseudoephedrine 7.5mg/5ml + Chlorphenamine 0.5mg/5ml: 10ml three times per day during 4 days
Experimental: Ivy Leaf (Hedera Helix Extract); Ivy Leaf (Hedera Helix Extract) 35 mg/5ml: 10ml three times per day during 4 days	Drug: Ivy Leaves Cough Liquid; Ivy Leaf (Hedera Helix Extract) 35 mg/5ml: 10ml three times per day during 4 days
Placebo Comparator: Placebo; Vitamins: 10ml three times per day during 4 days	Drug: Placebo; Vitamins: 10ml three times per day during 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cough severity	Change in cough severity measured by a cough numerical rating scale (0-10, higher scores mean higher cough severity)	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cough severity and duration	Change in cough severity and duration measured with the Cough Severity Diary	48 hours
Change in cough severity and duration	Change in cough severity and duration measured with the Cough Severity Diary	4 days
Change in cough severity and duration	Change in cough severity and duration measured with the Cough Severity Diary	10 days
Treatment safety	Number of adverse events	48 hours
Treatment safety	Number of adverse events	4 days
Treatment safety	Number of adverse events	10 days
Change in cough severity	Change in cough severity measured with the cough numerical rating scale (0-10, higher scores mean higher cough severity)	4 days
Change in cough severity	Change in cough severity measured with the cough numerical rating scale (0-10, higher scores mean higher cough severity)	10 days
Treatment failure	Categorical outcome: Yes: Persisting with a score ≥6 in the cough numerical rating scale (0-10) No: Not having cough or persisting with a score <6 in the cough numerical rating scale (0-10)	4 days
Treatment failure	Categorical outcome: Yes: Persisting with a score ≥6 in the cough numerical rating scale (0-10) No: Not having cough or persisting with a score <6 in the cough numerical rating scale (0-10)	10 days

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: UC CHRISTUS

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Actual): November 22, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: March 26, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cough; Codeine; Upper Respiratory Tract Infection; Levodropropizine; Hedera Helix
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Respiratory Tract Infections; Cough; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Codeine; dipropizine
• Other Study ID Numbers: 241001007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No