Fine Particle pMDI Formoterol/Beclomethasone in Asthmatics With and Without Spacer: Comparative Efficacy Evaluation (EFFECT-EV)

Randomized Clinical Trials to Compare Asthma Control Efficacy of the Fine-particle Combination Formoterol/Beclomethasone by pMDI Administered With and Without Spacer.

Adequate pharmacological treatment controls symptoms in most asthmatics. Pressurized metered dose inhalers (pMDI)are the most used drug delivery devices. Valved holding chambers of different types and sizes have also been developed for use in combination with pMDI. The therapeutic efficacy of treatment depends on the amount of inhaled particles. The chambers can optimize lung deposition as it obviates lung-hand coordination and retain larger particles. The aim of this study is to compare the efficacy of the fine particle combination pMDI Beclomethasone/Formoterol in asthma control,with or without the aid of a spacer in patients without adequate asthma control on medium to high-dose inhaled steroids associated with long acting beta adrenergic drugs. The hypothesis is that there is no clinical efficacy difference between the two forms of drug administration.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Device: Spacer; Device: Comparator

Detailed Description

This is a randomized, parallel controlled study with blind outcome evaluation to compare the efficacy of the fine particle combination Beclomethasone/Formoterol administered with or without valved holding chamber (Vortex, Pari Innovative Manufacturers, VA - USA.

Eligible asthma patients will begin a 2-weeks run-in period to optimize their control medication use and to learn the correct relief pMDI use without holding chamber. After the run-in, patients with non-controled asthma symptoms (ACT score 19 or under)in spite the use of medium to high dose inhaled steroids and LABA association and able to use correctly the pMDI will be randomized (block-randomization) to receive the test medication combination to be used with or without the spacer device (VORTEX). Patients will be evaluated after 30 and 60 days. At days 15 (+,- 2) and 45 (+,- 2) they will have an incentive phone call.

ACT score (translated and validated to portuguese - Brazil), FEV1 (Kit-Micro spirometer, Cosmed, Italy), pMDI use and clinical evaluation will be obtained at initial visit (visit 0), randomization visit (visit 1)and at 30 and 60 days (visits 2 and 3). Extra-medication allowed at run-in period will be inhaled beta-2 bronchodilators for relief an at treatment period inhaled beta-2 agonists for relief and systemic steroids for exacerbations, with antibiotics as needed.

Endpoint evaluations will be proceeded by a treatment blinded investigator.In order to keep the concealment, the evaluations will be held in a different room and the patients instructed not to comment on treatment.

Subjects will be excluded at the treatment period in case of severe asthma exacerbation (hospital or ICU recovery or systemic steroid used for more than 5 days). They will be excluded also in case of concomitant ailments at discretion of the attending physician. These patients will be excluded from the per-protocol evaluation but will be described.

Sample size was calculated taking into account a relevant ACT score difference of 3 points and a SD of 4.4 (SCHATZ M et all. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol 2006;117:549-56). In order to be able to detect this difference with α and β errors of 5% and 20% respectively, the investigators calculated 32 patients per group.

Statistical analysis will be carried according to data distribution by a professional statistician.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50740-520
      • Hospital das Clinicas - Universidade Federal de Pernambuco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult, age 18 to 65 years, both sexes;
2. Clinical diagnosis of moderate to severe persistent asthma;
3. Nonsmoker;
4. Agree to participate and sign the Informed Consent;
5. ACT Score <= 19
6. FEV1 <= 80% of predicted;
7. History of response to FEV1 greater than 10%;
8. Patients who are already using Inhaled steroids at medium to high doses (Beclomethasone, budesonide, fluticasone) with longa-acting beta2 agonists (formoterol or salmeterol)
9. Proper use of metered-dose inhaler (after orientation)

Exclusion Criteria:

1. Patient diagnosed with Chronic Obstructive Pulmonary Disease (COPD);
2. Current smokers or have stopped for less than 10 years;
3. Patients with a history of recent near-fatal asthma (less than 12 months);
4. Patients with a history of recent asthma hospitalization (last 6 months);
5. Patients with airway infection symptoms for less than 4 weeks;
6. Participation in any experimental study up to 1 (one) year from selection visit;
7. Hospitalization for any reason up to 8 weeks before selection visit;
8. History of liver, cardiac, renal, pulmonary or gastrointestinal diseases, epileptic, psychiatric or hematologic disorders, uncontrolled hypertension, rheumatology/orthopedic disorders that interferes with pMDI use;
9. Patients unable to properly use the pMDI during the selection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Spacer; Beclomethasone/Formoterol 100/6mcg/puff pMDI 2 puffs two times/day with the aid of a Valved Holding Chamber - VORTEX	Device: Spacer; Beclomethasone/Formoterol 100/6mcg pMDI 2 puffs two times/day with the aid of a Valved Holding Chamber - VORTEX; Other Names: BECLOMETHASONE EXTRA-FINE; FORMOTEROL; FOSTAIR; INNOVAIR; VORTEX
ACTIVE_COMPARATOR: Comparator; Beclomethasone/Formoterol pMDI 100/6mcg/puff pMDI 2 puffs two times/day without the aid of a Valved Holding Chamber - VORTEX	Device: Comparator; Beclomethasone/Formoterol 100/6mcg pMDI 2 puffs two times/day without the aid of a Valved Holding Chamber - VORTEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Asthma Control Test Score	The primary endpoint is the difference in the change of ACT score between groups 8 weeks after randomization compared to pre-randomization.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Forced Expiratory Volume in the first second (FEV1)	The secondary endpoint is the difference in the change on FEV1 between groups at 4 and 8 weeks after randomization compared to pre-randomization.	4 and 8 weeks

Collaborators and Investigators

• Sponsor: Universidade Federal de Pernambuco
• Collaborators: Universidade Federal do vale do São Francisco
• Investigators: Principal Investigator: Jose A Rizzo, PhD, MD, Universidade Federal de Pernambuco

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 17, 2011
• First Posted (ESTIMATE): October 18, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 29, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Asthma; Efficacy; Formoterol; Beclomethasone; pMDI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Beclomethasone; Formoterol Fumarate
• Other Study ID Numbers: PTC 034/11