Higher Versus Standard Dose of Amoxicillin-clavulanate in Pediatric PBB

Higher Versus Standard Dose of Amoxicillin-clavulanate in Pediatric Protracted Bacterial Bronchitis: a Randomized Controlled Study.

Chronic wet cough is one of the most common symptoms of respiratory diseases in children. Protracted bacterial bronchitis (protracted bacterial bronchitis, PBB) is the most common cause of chronic wet cough in children. Potassium amoxicillin clavulanate is the recommended drug for the treatment of PBB, but there is not enough evidence to date on the dose and course of treatment. investigate the efficacy of different doses of amoxicillin clavulanate sodium in the treatment of chronic bacterial bronchitis in children. The methods of this study are summarized as following:

1. Screening cases of chronic wet cough in children aged 2 to 6 years old who came to our hospital for treatment. Those diagnosed as PBB were included in this study, after obtaining the written informed consent from their parents or guardians.
2. The enrolled patients were randomly divided into high-dose (90mg/kg/d) and standard dose (60mg/kg/d) amoxicillin clavulanate potassium treatment group.
3. Medical history data of enrolled patients and daily cough score data were collected.
4. Assess the cough remission rate within two weeks and recurrence rate within 6 months in both groups.

Study Overview

• Status: Unknown
• Conditions: Protracted Bacterial Bronchitis
• Intervention / Treatment: Drug: Amoxicillin-Clavulanate 200 Mg-28.5 Mg Oral dry suspension

Detailed Description

Chronic cough is one of the common reasons for children seeking medical treatment. In children, chronic cough is associated with impaired quality of life, multiple doctor visits, and adverse effects from inappropriate use of medications. Protracted bacterial bronchitis (PBB) is the most common cause of chronic wet cough in children. Most PBB has a good prognosis, but the persistence of PBB can lead to chronic suppurative lung disease, bronchiectasis and chronic obstructive pneumonia. Therefore, PBB must be timely diagnosed, standardized treatment and strict monitoring to avoid the progression of bronchiectasis and chronic obstructive pulmonary disease.

As in children with chronic wet cough, H. influenzae was the most common pathogen cultured from children with PBB. The other commonly detected bacteria are Strep. pneumoniae and M. catarrhalis and while Staphylococcus aureus. Amoxicillin clavulanate is the most commonly recommended drug for the treatment of PBB, but there is no sufficient evidence for the dose and course of treatment. Therefore, the purpose of this study was to elucidate the optimal dose of amoxicillin clavulanate potassium in the treatment of PBB. It is expected that 100 cases will be included and divided into high-dose group and routine dose group. After grouping, the corresponding dose of amoxicillin clavulanate potassium dry suspension will be prescribed according to the grouping conditions. Patients in high-dose group will receive 90mg/kg/d and the regular dose was 60mg/kg/d, which were taken orally twice a day. Medical history data and daily cough score data of enrolled patients were collected to assess the cough remission rate and recurrence rate within 6 months in both groups.

The research content:

1. Screening cases of chronic wet cough in children aged 2 to 6 years old who came to our hospital for treatment. Those diagnosed with PBB were included in this study after obtaining the written informed consent of their parents or guardians.
2. The enrolled patients were randomly divided into high-dose (90mg/kg/d) and routine dose (60mg/kg/d) amoxicillin clavulanate potassium treatment group.
3. Medical history data of enrolled patients and daily cough score data were collected.
4. Assess the cough remission rate and recurrence rate within 6 months in both groups.

Study design A randomized controlled study for children with protracted bacterial bronchitis

Therapeutic regimens

1. In high-dose group, patients take dry suspension of amoxicillin clavulanate potassium 45 mg/kg/ time (amoxicillin) orally twice a day, total daily dose not exceeding 2 g, and the course of treatment is two weeks.
2. In standard dose group, patients take dry suspension of amoxicillin clavulanate potassium 30 mg/kg/ time (amoxicillin) orally twice a day, total daily dose not exceeding 2 g, and the course of treatment is two weeks.

Effect evaluation

1. Major outcome measure: "cough remission" rate, defined as a more than 75% reduction in verbal category descriptive (VCD) cough score at the end of the study compared to the baseline score at enrollment, or cough cessation for more than 3 days during the study period. The basic score refers to the average VCD of the first two days (-1 and -2 days). The score at the end of the study was the mean score for the first two days (15,16 days) after the 14-day study period.
2. Secondary outcome measures: the absolute change in VCD score and the incidence of adverse events during the study period.

Safety assessment Safety issues will be evaluated before the enrollment and during the follow-up. it mainly included the analysis of meaningful clinical symptoms and adverse events, and the comparison of laboratory tests before and after the treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children diagnosed with first-onset PBB
• Subjects and their guardians agree to participate in the study and sign an informed consent

Exclusion Criteria:

• Seriously delayed development of the nervous system;
• With severe underlying diseases: such as severe neuromuscular diseases, immunodeficiency, malnutrition, heart diseases, congenital respiratory system malformation, and other diseases of the heart, brain, liver, kidney and blood system;
• Other diseases that can cause chronic wet cough, including chronic rhinitis, sinusitis, interstitial lung disease, and clinical suspicion of bronchiectasis;
• With poor compliance and expected difficulty in completing the study;
• Other conditions considered inappropriate by the researcher.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high-dose group; patients take dry suspension of amoxicillin clavulanate potassium 45 mg/kg/ time (amoxicillin) orally twice a day, total daily dose not exceeding 2 g, and the course of treatment is two weeks.	Drug: Amoxicillin-Clavulanate 200 Mg-28.5 Mg Oral dry suspension; dry suspension of amoxicillin clavulanate potassium; Other Names: Amoxicillin and Clavulanate Potassium for Suspension
Experimental: standard dose group; patients take dry suspension of amoxicillin clavulanate potassium 30 mg/kg/ time (amoxicillin) orally twice a day, total daily dose not exceeding 2 g, and the course of treatment is two weeks.	Drug: Amoxicillin-Clavulanate 200 Mg-28.5 Mg Oral dry suspension; dry suspension of amoxicillin clavulanate potassium; Other Names: Amoxicillin and Clavulanate Potassium for Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cough remission rate	defined as a more than 75% reduction in VCD cough score at the end of the study compared to the baseline score at enrollment, or cough cessation for more than 3 days during the study period.	within two weeks of inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the absolute change in VCD score	The basic score refers to the average VCD of the first two days (-1 and -2 days). The score at the end of the study was the mean score for the first two days (15,16 days) after the 14-day study period.	within two weeks of inclusion
the incidence of adverse events	the incidence of any adverse event and severe adverse event	through their followup completion, an average of half year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Principal Investigator: Hai-lin Zhang, MD, Second Affiliated Hospital of Wenzhou Medical Universitiy

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: May 5, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: SAHoWMU-CR2018-06-121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No