Clinical trial NCT02060149: The Effect of Nebulization of Alkaline Solution on Treating XDRAB Pneumonia With C/S Plus Minocycline
Official title: The Effect of Nebulization of Alkaline Solution on Treating Extensively Drug Resistant A. Baumannii Pneumonia With Cefoperazone and Sulbactam Plus Minocycline: A Multi-center Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Pneumonia
Keywords: Extensively Drug Resistant A. Baumannii
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2014-02-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The mortality of pneumonia with extensively drug resistant Acinetobacter baumannii (XDRAB) is still high, even if these patients received certain strong anti-infection treatment such us the combination of cefoperazone-sulbactam (C/S) and minocycline. Health airway lining fluid is mildly alkaline but airway acidification usually appears for the infection of XDRAB. The hypothesis is offered that the biologic activity of XDRAB might be inhibited if the circumstance including pH is changed. In the vitro study we observed that the inhibit effect of antibiotics on XDRAB growth was improved significantly by alkaline solution within the scope of physiology. So the aim of this clinical study is to explore the effects of nebulization of alkaline Solution on C/S plus minocycline on the pneumonia with XDRAB.

Detailed description: Pneumonia patients with XDRAB are eligible for this multicenter study, do not meet the exclusion criteria and will sign the informed consent. They will received the anti-infection protocol with Cefoperazone/ sulbactam 3.0g（intravenous infusion, q8h or q6h) combined with minocycline doxycycline 100mg (oral, q12h). All enrolled patients were randomly divided into three groups according to the difference in pH value of aerosol inhalation with sodium bicarbonate solution. Group one is blank-control and patients will received usual antibiotic treatment without inhalation. The pH value in group two is 7.4 and that in group is 7.8. Each time the volume of aerosol solution is 5ml, q8h. The average course of treatment will be two weeks. Clinical indexes will be collected including vital signs, pulmonary rales, cough level, expectoration level, sputum color,blood count, arterial blood gas, biochemical parameters, chest X-ray score, APACHE II score, clinical pulmonary infection score, ECG, sputum culture, et al.The primary endpoints are pathogenic clearance rate and recovery rate. The secondary end point is adverse reaction rate.

Eligibility criteria: Inclusion Criteria:

* Age: 18 to 75 years old, male or female
* The pneumonia patients met the diagnostic criteria, and clinical pulmonary infection score (CPIS) ≥ 5;
* The sputum bacteriology detection only prompted Acinetobacter baumannii culture for pathogens concentration meets the diagnostic criteria of the Chinese hospital-acquired pneumonia diagnosis and treatment guidelines, 2002 edition of "Acinetobacter baumannii and susceptibility results show only 1 to 2 sensitive to antimicrobial drugs (polymyxin, minocycline or tegafur doxycycline);
* Cephalosporins or tetracyclines drug treatment without a history of allergies and contraindications;
* Be able to accept inhalation therapy.
* Informed consent gained

Exclusion Criteria:

* Refused to accept inhalation therapy
* Renal insufficiency, creatinine clearance (Cockcroft-Gault formula) (CLcr) 15 ml / min or less;
* Liver dysfunction, defined as Child-Pugh score B or C
* Within one week before the start of cefoperazone sulbactam, minocycline treatment.

Primary outcomes:
measure: Pathogenic Clearance rate and recovery rate
timeFrame: one treatment course for about two weeks
Secondary outcomes:
measure: adverse reaction rate
timeFrame: one treatment course for about two weeks
Other outcomes:
measure: hospital time and mortality
timeFrame: about four weeks
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
Study officials:
affiliation: first affiliated hospital, fourth military medical university
name: liqiang song, doctor
role: PRINCIPAL_INVESTIGATOR
References: