Efficacy Of Doxophylline As A Sparing Treatment For Inhaled Corticosteroids In Mexican Children With Asthma

Phase 3

• Conditions: Asthma Chronic; Asthma in Children
• Interventions: Drug: Doxophylline; Drug: Budesonide

• Registration Number: NCT03879590
• Lead Sponsor: Universidad Autonoma de Nuevo Leon

Brief Summary

This study evaluated the efficacy of doxophylline as a steroid sparing treatment in Mexican children with asthma treated with medium ir high doses of inhaled corticosteroids (ICS). It is a cross over study in which both groups of patients will receive doxophylline plus a lower steroid dose maintaining the same treatment step according to GINA guidelines, one group will maintain the same treatment dose while the other will start with doxophylline with the lower ICS dose, and by the middle of the study both groups will interchange treatment schemes.

Detailed Description

Inhaled corticosteroids (ICS) are first-line drugs for the treatment of persistent asthma. The effectiveness of existing ICS is excellent; however, a number of questions remain regarding its possible adverse effects, despite the fact that the use of the inhalation route has allowed the minimization of the systemic exposure to these drugs. Methylxanthines are widely used in the treatment of asthma. It is one of the few medications for asthma that can be administered orally. They are useful especially in patients who cannot adapt to inhaled medications. Methylxanthines are unique in exhibiting dual-function properties by inducing bronchodilation and having anti-inflammatory and immunomodulatory effects. Theophylline is the oldest methylxanthine and non-specifically inhibits phosphodiesterase, it is a little used drug because it has many adverse effects with lower therapeutic index. Doxophylline is a drug of the family of methylxanthines, with a similar efficacy compared to theophylline when applied in the treatment of various respiratory diseases, but with better tolerability profile. Doxophylline has been shown to be a bronchodilator and anti-inflammatory drug with a wider therapeutic window than other methylxanthines. Clinical studies have reported that doxophylline is more effective in improving lung function tests in adults and children, as well as in decreasing clinical symptoms, reducing the incidence of adverse effects and the need of emergency bronchodilators, with a better profile in terms of safety and it has been demonstrated that doxophylline potentially reduces the need for corticosteroids.

Study Timeline

• Study First Submitted: 2018-11-25
• Status Verified: 2019-03
• Study First Submitted QC: 2019-03-14
• Last Update Submitted: 2019-03-14
• Study First Posted: 2019-03-19
• Last Update Posted: 2019-03-19
• Study Start: 2019-05
• Primary Completion: 2019-09
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Mexican patients between 6 and 16 years old.
2. Clinical diagnosis of asthma according to the current guidelines of the Global Asthma Initiative (GINA) 2018.
3. Patients with asthma treated with budesonide at medium or high doses during (GINA guidelines´ steps 3 or 4) at least two months before the first study visit. Budesonide medium dose: 200-400 mcg / day (6-11 years) and 400-800 mcg / day (> 12 years). Budesonide high dose: > 400 mcg / day (6-11 years) and > 800 mcg / day (> 12 years).

Exclusion Criteria

1. Patients <6 or ≥16 years of age.
2. Patients with <16 kg of body weight.
3. Patients who have had an asthma exacerbation that required treatment with systemic corticosteroids (oral, intramuscular or intravenous) during the 2 months prior to the first study visit.
4. Patients who have presented an asthma exacerbation that required hospitalization during the 2 months prior to the first study visit.
5. Any other chronic lung disease that could impair lung function evaluation.
6. Cardiovascular, infectious, metabolic or neoplastic disease that could interfere with the evaluation of the patient.
7. Current use of drugs that interact with doxophylline: other xanthines, ephedrine or other sympathomimetics, erythromycin, troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, two months prior vaccination, propranolol, phenytoin or other anticonvulsants.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Budesonide and Doxophylline	Budesonide	Budesonide at the same dose in which the subject is currently treated (GINA step 3 or 4) plus doxophylline at a dose of 18 mg / kg per day
Low budesonide and Doxophylline	Doxophylline	Reduced dose of inhaled budesonide (GINA step down) plus doxophylline to a dose of 18 mg / kg per day, maximum of 800 mg / day (Group B)
Budesonide and Doxophylline	Doxophylline	Budesonide at the same dose in which the subject is currently treated (GINA step 3 or 4) plus doxophylline at a dose of 18 mg / kg per day
Low budesonide and Doxophylline	Budesonide	Reduced dose of inhaled budesonide (GINA step down) plus doxophylline to a dose of 18 mg / kg per day, maximum of 800 mg / day (Group B)

Primary Outcome Measures

Name	Time	Method
Changes in the values of the forced expiratory volume on the first second	4 weeks	Changes in the values of FEV1 (FEV1 in percent predicted) by comparing the baseline to subsequent evaluations.

Secondary Outcome Measures

Name	Time	Method
Use of systemic corticosteroids	4 weeks	- The use of systemic corticosteroids for at least 3 days for the treatment of an asthma exacerbation according to the data collected in the patient's diaries.
Clinical asthma control assessment	4 weeks	Differences in clinical asthma control assessment with a visual analogue scale (minimum score is 1, maximum score is 10,) comparing the baseline to follow-up evaluations.
Changes on the exhaled breath temperature	4 weeks	-Differences in values exhaled breath temperature measured in Celsius degrees with the X-halo device, comparing the baseline to follow-up evaluations.
Asthma exacerbations	4 weeks	Number of asthma exacerbations defined as acute episodes of progressively worsening shortness of breath, coughing, wheezing, and chest tightness or any combination thereof for at least 3 days, reported on the patient´s symptoms log.
Use of rescue therapy	4 weeks	The use of rescue therapy defined as daily average of inhalations per day according to the data collected in the patient's diaries.