Clinical trial NCT02883582: Adjuvant Therapy for Severe Asthma by an Oxyhydrogen Generator With Nebulizer
Official title: Adjuvant Therapy for Severe Asthma by an Oxyhydrogen Generator With Nebulizer: A Multi-centric, Randomized, Parallel-control and Double-blinded Clinic Study on Effectiveness and Safety
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Asthma
Keywords: asthma ,hydrogen
Lead sponsor: Shanghai Asclepius Meditec Inc.
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Guangzhou Medical University
name: Second Affiliated Hospital of Guangzhou Medical University
name: The Second Hospital of Hebei Medical University
name: Tianjin Medical University General Hospital
name: West China Hospital
First posted: 2016-08-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose for the trial is intended to evaluate safety and effectiveness of an oxyhydrogen generator with nebulizer in an adjuvant therapy for patients with severe asthma.

Detailed description: The oxyhydrogen generator with nebulizer in (treatment group) or control group was applied randomly for the patients with severe asthma in this study, then the therapeutic effects from both treatment and control groups were analyzed and evaluated to verify its safety and effectiveness.This study is a multi-center, randomized, double-blind study. Each patient was expected to participate in the trial for 104±3 day.The screening period was 14±1 days, and the subjects would continue to be applied with the previous asthma treatment scheme. The primary objective was to collect the baseline data related to the subjects.The patients would receive 30±1 day of treatment with the product; after that, observation of 60±1 days was required.Total patients number is 150 cases, of which 75 cases are treatment group and the others are control group.All cases respectively are distributed in 5 clinical hospitals.

Eligibility criteria: Inclusion Criteria:

1. Age range: ≥18 years old but ≤65 years old; sex unlimited;
2. The subjects were required to be suffered with asthma for 6 months at least by clinical diagnosis by the respirologist based on the international standards (GINA2012).There was the support of one of the following objective evidences in screening and treatment or five years before the treatment:

   * It was the positive reaction in the methacholine provocative test (for the patients not applied with inhaled corticosteroid (ICS) were required at PC20\<8mg/mL and PD20\<0.7mg; for the patients applied with ICS were required at PC20\<16mg/mL or PD20\<1.4mg);

     * The airway reversibility test, with a positive reaction, was defined asΔFEV1.0% at a basis FEV1.0≥200mL at 30 minutes after 400μgsalbutamol aerosol (mist-storing bottle might be used deliberately) was inhaled; ③ The peak expiratory flow (PEF) aberration rate\>20% (that is, the difference or average value of maximum and minimum PEFs times 100); it was measured for seven days successively;

       * The reaction record after asthma maintenance treatment for one course of treatment (e.g. four weeks) (defined as ΔFEV1.0 and its absolute value≥200mL);
3. According with severe asthma diagnosis: The drug therapy was required for Level-4 and 5 asthma according to GINA Guide in the past year (The large dose of ICS combined LABA or leukotriene modifier/theophyline), or the systemic corticosteroid treatment lasted at ≥50% of the time to prevent from the "uncontrollable" asthma; or the "uncontrollable" asthma still occurred even if in above treatment. The uncontrollable asthma should meet one of the following requirements at least:

   * Symptom control difference: ACQ\>1.5, and ACT\<20 (or "Non-good control" in GINA Guide);

     * Frequent severe attack: Receiving systemic corticosteroid treatment for more than twice in the past year (over three days each time); ③ Serious attack: Hospitalizing once in ICU or mechanical ventilation at least in the past year; ④ Airway limitation: After bronchodilator was stopped properly, FEVl.0%\<80% (FEV/FVC decreased to be less than lower limit of the normal value). The controlled asthma deteriorated at the decrement of above large dose ICS or systemic corticosteroid (or combined biologic agent);
4. The subjects or their legal agents could understand the trial objectives, demonstrating the compliance to the trail scheme, and signed the Informed Consent Form.

Exclusion Criteria:

1. The subjects at a body mass index\>38kg/m2, or a weight\<40kg;
2. The subjects' smoking amount\>10 packages times the year number (e.g. number of cigarettes × the number of years for smoking/20);
3. Based on clinical interview, experience or screening inspection results, the subjects should participate in this trial improperly if the doctor responsible for the trial believed there was risk when they participated in the trial, or the research results were affected;
4. The subjects who had the recreational drug abuse history or other allergic history, but the doctor responsible for the trial believed these subjects limited by the history could participated in the trial;
5. The women subjects who were in the pregnancy or suckling period, or six weeks at least after delivery, or stopped breastfeeding for six weeks. If the women subjects were found to be pregnant in receiving one inspection, then, the inspection data for this item should be rejected in analysis;
6. The subjects ever participated in the study on a new drug or any other drugs, and were within 3 months for the first administration, or every participated in one research involved in invasive operation within 3 months. Any research evaluation should be put off to three months later in the first administration or invasive operation when they participated in the research. It was approved by the steering committee if the subjects participating in other researches were included in trial groups or continued participating in this research;
7. The investigator believed the subjects showed the risk of non-compliance with research procedures;
8. The subjects had the mental disease history resulting in loss of active ability in the recent period;
9. The following disease history or evidences demonstrated within two weeks in baseline assessment that the subjects suffered upper or lower respiratory infections or related symptoms (including common cold) (the assessment should be put off);
10. The subject changed the asthmatic drugs within four weeks before the screening;
11. The subject suffered the asthma attack in the month prior (administered with systemic corticosteroid or temporarily increasing oral corticosteroid at three days of stable base dose at least);
12. Other important diagnoses possibly similar to asthma or complicated asthma, especially respiratory dysfunction, panic attack and evident social psychological problems (if these diagnoses were seen as the patient's main symptoms rather than the symptoms except severe asthma);
13. Other severe primary pulmonary diseases, especially pulmonary embolism, pulmonary hypertension, interstitial pulmonary disease and lung cancer;
14. The subjects with emphysema and bronchiectasis should be excluded only when these diagnoses are considered as their main symptoms rather than other symptoms except severe asthma;
15. The subjects who were diagnosed with other chronic inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis) except asthma.

Primary outcomes:
measure: differentials from Mini Asthma Quality of life questionnaire (Mini AQLQ)
timeFrame: at 3 months
Secondary outcomes:
measure: differentials from asthma control questionnaire
timeFrame: at 3 months
measure: differentials from asthma control test (ACT)
timeFrame: at 3 months
measure: differentials from Peak Expiratory Flow (PEF) daily aberration rate
timeFrame: at 3 months
measure: differentials from airway resistance measurement
timeFrame: at 3 months
measure: differentials from number of asthma acute attacks
timeFrame: at 3 months
measure: differentials from number of uses of first-aid drugs
timeFrame: at 3 months
measure: differentials from Special allergens
timeFrame: at 3 months
measure: differentials from blood routine examination
timeFrame: at 3 months
measure: differentials from serum C reactive protein (CRP)
timeFrame: at 3 months
measure: differentials from liver function examination
timeFrame: at 3 months
measure: differentials from renal function examination
timeFrame: at 3 months
measure: differentials from electrolyte test
timeFrame: at 3 months
measure: differentials from routine urine test
timeFrame: at 3 months
measure: differentials from 12-lead ECG test
timeFrame: at 3 months
measure: differentials from urine pregnancy test for fertile women
timeFrame: at 3 months
measure: differentials from pulmonary function
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-6(IL-6)
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-8( IL - 8)
timeFrame: at 3 months
measure: differentials from Baseline in Serum tumor necrosis factor-a(TNF-a)
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-4( IL - 4)
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-5( IL - 5)
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-13( IL - 13)
timeFrame: at 3 months
measure: differentials from Baseline in Serum interleukin-17( IL - 17)
timeFrame: at 3 months
measure: differentials from induced sputum test
timeFrame: at 3 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: the First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: China, Guangdong First Affiliated Hospital of Guangzhou Medical University
name: Nanshan Zhong, academician
role: STUDY_CHAIR
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