The Effect of Nebulization of Alkaline Solution on Treating XDRAB Pneumonia With C/S Plus Minocycline (NAEDRAP)

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

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.

Study Overview

• Status: Unknown
• Conditions: Pneumonia
• Intervention / Treatment: Drug: C/S plus minocycline.; Drug: No nebulization; Drug: nebulization with pH 7.4 solution; Drug: nebulization with pH 7.8 solution

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: no nebulization; Antibiotics protocol is C/S plus minocycline. That is Cefoperazone/ sulbactam 3.0g（intravenous infusion, q8h or q6h) combined with minocycline doxycycline 100mg (oral,q12h).No nebulization will given to these patients.	Drug: C/S plus minocycline.; Cefoperazone/ sulbactam 3.0g（intravenous infusion, q8h or q6h) combined with minocycline doxycycline 100mg (oral, q12h).; Other Names: CEFOPERAZONE SODIUM AND SULBACTAM SODIUM FOR INJECTION; Drug: No nebulization; No nebulization will be given to the patients.; Other Names: sham
Active Comparator: nebulization with pH 7.4 solution; Patients will received the same antibiotics protocol with C/S plus minocycline and nebulization with pH 7.4 solution(Each time the volume of aerosol solution is 5ml, q8h).	Drug: C/S plus minocycline.; Cefoperazone/ sulbactam 3.0g（intravenous infusion, q8h or q6h) combined with minocycline doxycycline 100mg (oral, q12h).; Other Names: CEFOPERAZONE SODIUM AND SULBACTAM SODIUM FOR INJECTION; Drug: nebulization with pH 7.4 solution; Patients will receive the nebulization with Sodium Bicarbonate of pH 7.4 (Each time the volume of aerosol solution is 5ml, q8h).; Other Names: Sodium Bicarbonate
Experimental: nebulization with pH 7.8 solution; Patients will received the same antibiotics protocol with C/S plus minocycline and nebulization with pH 7.8 solution(Each time the volume of aerosol solution is 5ml, q8h).	Drug: C/S plus minocycline.; Cefoperazone/ sulbactam 3.0g（intravenous infusion, q8h or q6h) combined with minocycline doxycycline 100mg (oral, q12h).; Other Names: CEFOPERAZONE SODIUM AND SULBACTAM SODIUM FOR INJECTION; Drug: nebulization with pH 7.8 solution; Patients will receive the nebulization with Sodium Bicarbonate of pH 7.8 (Each time the volume of aerosol solution is 5ml, q8h).; Other Names: Sodium Bicarbonate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathogenic Clearance rate and recovery rate	one treatment course for about two weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
adverse reaction rate	one treatment course for about two weeks

Other Outcome Measures

Outcome Measure	Time Frame
hospital time and mortality	about four weeks

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: liqiang song, doctor, first affiliated hospital, fourth military medical university

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): March 1, 2015
• Study Completion (Anticipated): April 1, 2015

Study Registration Dates

• First Submitted: March 10, 2013
• First Submitted That Met QC Criteria: February 9, 2014
• First Posted (Estimate): February 11, 2014

Study Record Updates

• Last Update Posted (Estimate): February 11, 2014
• Last Update Submitted That Met QC Criteria: February 9, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Extensively Drug Resistant A. Baumannii
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Pharmaceutical Solutions; Minocycline; Sulbactam; Cefoperazone
• Other Study ID Numbers: xjhx-song1