Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT04879030 |
Other study ID # |
HPMU.01.04.21 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2/Phase 3
|
First received |
|
Last updated |
|
Start date |
January 1, 2020 |
Est. completion date |
December 30, 2020 |
Study information
Verified date |
February 2020 |
Source |
Haiphong University of Medicine and Pharmacy |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The investigators hypothesized that the empirical use of fluoroquinolones together with
beta-lactam antibiotics will change their therapeutic success in patients with acute
exacerbations of COPD compared to that in patients in whom a single beta-lactam treatment was
used. The main goal of this study was to compare the clinical and bacterial success from the
use of a combination of beta-lactam and fluoroquinolone antibiotics with that of a single
beta-lactam treatment, in adult patients with COPD exacerbations.
Description:
The study protocols were reviewed and approved by the Hai Phong International Hospital
Institutional Review Board, Vietnam. The study was conducted in accordance with the
Declaration of Helsinki and the International Conference on the Harmonization of the
Technical Requirements for the Registration of Pharmaceuticals for Human Use - Good Clinical
Practice guidelines. All subjects gave written informed consent before study initiation.
The participants consisted of patients aged over 45 years, diagnosed with COPD stages I-IV as
stated by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 13, with acute
exacerbations (onset of signs under 14 days as defined by Anthonisen et al. 14: type 1
[increased dyspnea, increased sputum volume, and sputum purulence] or type 2 [involved two or
three symptoms that needed hospitalization]), the incompetence to use medication by mouth,
fever (temperature over 38.5°C), antibiotic usage for longer than 1 day, treatment with
systemic administration of corticosteroids (dosage equivalent to more than 30 mg of
prednisolon over four days), signs of pneumonia on radiographs, history of mechanical
ventilation during acute exacerbations of COPD in the past, recently detected or unresolved
pulmonary malignancy, other infectious diseases requiring antibiotic treatment, and kidney
failure.
Randomization and Intervention This was an open-label, randomized study using two types of
treatments. Participants were divided into two groups using a randomization procedure. Within
24 hours of admission, patients were assigned randomly to two groups, one to receive a course
of single-antibiotic therapy with only beta-lactam antibiotics and the other to get
concomitant antibiotic treatment, defined as the use of two antibiotics, including one
beta-lactam antibiotic and one fluoroquinolone. The beta-lactam antibiotics with activity
against gram-negative bacilli in this study included piperacillin-tazobactam,
ticarcillin-clavulanate, imipenem-cilastin, meropenem, ertapenem, ceftazidime, ceftriaxone,
cefotaxime, and cefixime. The fluoroquinolone antibiotics included ciprofloxacin,
levofloxacin, and moxifloxacin. The other COPD medications were continued. When antibiotic
therapy failed, the attending physician had the right to reevaluate the clinical status and
to replace the antibiotic therapy in the study with a more appropriate treatment. Safety was
recorded daily with the support of a clinical pharmacist to report adverse events. Patient
data is stored in electronic medical records.
Outcomes and Follow-Up On days 1, 10, and 20, patients were evaluated clinically, and blood
was drawn, collected and the levels of C-reactive protein (CRP, Beckman Coulter Inc.,
Fullerton, CA) measured. Pulmonary function testing was done and expectorated sputum samples
were collected. The symptoms were scored by using the visual analogue scale (VAS) for
shortness of breath, tiredness, cough, and sputum color. The specific scores for each symptom
ranged from 1 to 10 15. Separate and total scores were calculated.
The primary endpoint was a clinical outcome on day 20, as stated by Chow et al. 16.
Successful treatment was defined as a cure (completely resolved signs and symptoms related to
exacerbations) or improvement (resolved or decreased symptoms and signs without new symptoms
or signs related to infection). Treatment failure was defined as the failure to address
symptoms and signs, worsening of symptoms and signs, the appearance of new symptoms and signs
related to the primary or a new infection, or death.
Secondary endpoints included clinical outcome on day 10 and clinical success on days 10 and
20, based on lung function (forced expiratory volume in one second [FEV1]), serum CRP,
symptoms, and microbiological responses.