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

NCT ID: NCT03879590

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2019-12-31

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.

Conditions

Asthma Chronic; Asthma in Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Budesonide and 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

Group Type: EXPERIMENTAL

Doxophylline

Intervention Type: DRUG

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Budesonide

Intervention Type: DRUG

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Low budesonide and 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)

Group Type: ACTIVE_COMPARATOR

Doxophylline

Intervention Type: DRUG

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Budesonide

Intervention Type: DRUG

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Interventions

Doxophylline

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Intervention Type: DRUG

Budesonide

Both groups will receive doxophylline one group will maintain the ICS dose and the other group will receive a reduced ICS dose (Maintaining the same GINA treatment step). After 4 weeks both groups will interchange treatment scheme.

Intervention Type: DRUG

Other Intervention Names

There is no other intervention names; There is no other intervention names

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad Autonoma de Nuevo Leon

OTHER

Sponsor Role: lead

Responsible Party

Sandra Nora Gonzalez Diaz

Dra. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sandra Nora González-Díaz, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Autónoma de Nuevo León

Central Contacts

Carlos Macouzet-Sánchez, Dr.

Role: CONTACT

dr.macouzet@gmail.com

+528183462515

References

Lal D, Manocha S, Ray A, Vijayan VK, Kumar R. Comparative study of the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and chronic obstructive pulmonary disease. J Basic Clin Physiol Pharmacol. 2015 Sep;26(5):443-51. doi: 10.1515/jbcpp-2015-0006.

Reference Type: BACKGROUND

PMID: 25894641 (View on PubMed)

Margay SM, Farhat S, Kaur S, Teli HA. To study the efficacy and safety of doxophylline and theophylline in bronchial asthma. J Clin Diagn Res. 2015 Apr;9(4):FC05-8. doi: 10.7860/JCDR/2015/12438.5743. Epub 2015 Apr 1.

Reference Type: BACKGROUND

PMID: 26023566 (View on PubMed)

Rajanandh MG, Nageswari AD, Ilango K. Assessment of various second-line medications in addition to inhaled corticosteroid in asthma patients: a randomized controlled trial. Clin Exp Pharmacol Physiol. 2014 Jul;41(7):509-13. doi: 10.1111/1440-1681.12239.

Reference Type: BACKGROUND

PMID: 24738981 (View on PubMed)

Riffo-Vasquez Y, Venkatasamy R, Page CP. Steroid sparing effects of doxofylline. Pulm Pharmacol Ther. 2018 Feb;48:1-4. doi: 10.1016/j.pupt.2017.10.008. Epub 2017 Oct 16.

Reference Type: RESULT

PMID: 29031617 (View on PubMed)

Rajanandh MG, Nageswari AD, Ilango K. Pulmonary function assessment in mild to moderate persistent asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide: a randomized controlled study. Clin Ther. 2014 Apr 1;36(4):526-33. doi: 10.1016/j.clinthera.2014.02.006. Epub 2014 Mar 17.

Reference Type: RESULT

PMID: 24650447 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

DOXO

Identifier Type: -

Identifier Source: org_study_id