UMIN-CTR Clinical Trial

Public title

Clinical Efficacy of Cefditoren Pivoxil for Exacerbation of Chronic Obstructive Pulmonary Disease

Acronym

Clinical Efficacy of CDTR-PI for COPD exacerbation

Scientific Title

Clinical Efficacy of Cefditoren Pivoxil for Exacerbation of Chronic Obstructive Pulmonary Disease

Scientific Title:Acronym

Clinical Efficacy of CDTR-PI for COPD exacerbation

Region

Japan

Condition

Patients with COPD exacerbation and risk factors leading to severe, refractory infection

Classification by specialty

Medicine in general	Pneumology	Infectious disease

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the efficacy of CDTR-PI (200 mg,3 times/day for 7 days) in patients with COPD exacerbation who can be treated on an outpatient basis or with oral antimicrobial agents under actual conditions of use

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

- Clinical efficacy at 5-10 days after completing administration (judgment of cure)
- Adverse events during the evaluation period (If causality cannot be denied: adverse drug reaction)

Key secondary outcomes

- Clinical efficacy at completion of administration (efficacy rate)
- Clinical efficacy 3 days after administration (early evaluation of drug efficacy)
- Bacterial disappearance rate 5-10 days after completing administration

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

No treatment

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Administered drug: Cefditoren pivoxil (trade name: Meiact MS Tablets 100 mg).
Administration method: 200 mg (potency) (2 tablets), orally administered postprandially, three times per day.
Administration period: 7 days.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1)Location for treatment:
Outpatient or in-hospital.
2)Diagnostic criterion for COPD:
A pulmonary function test was conducted in the past 12 months and the latest stable forced expiratory volume in 1 second (FEV1.0/FVC) is under 70%.
3)Risk factors associated with severe, refractory infection.
At least one of the following factors is present.
(1) age: 65 years or older.
(2) COPD treatment history of at least 1 year.
(3) At least 2 exacerbations of infection in the past year.
(4) Reduced pulmonary function when free of infection.
Criteria for reduced pulmonary function are as follows:
- Oxygen therapy necessary
- Pulmonary function test showing %FEV1.0 of under 80%
- PaO2 or under 65 Torr (SpO2 or under 92%)
- etc.
(5) History of respiratory management using a mechanical ventilator.
(6) Cardiovascular disease, diabetes, renal disorder or various malignant diseases that require treatment as underlying disorders.
(7) Connective tissue disease, etc., that might impact infections.
4)Diagnostic criteria for exacerbation of COPD
(1)Mandatory condition: Both (a) and (b) must be met.
(a)New onset of coughing/sputum or increase in the amount of sputum or worsening of purulence.
(b)CRP elevation (or over 0.7 mg/dL, or exceeding the institution's upper limit) or increase in peripheral WBCs (or over 8,000/mm3, or exceeding the institution's upper limit).
(2)Selected criteria: It is desirable that the following conditions be met:
(a)Availability of high-quality samples (P sputum) that are likely to enable identification of the causative organism(s).
(b)Fever: or over 37 degree Centigrade (axillary measurement).
(c)General malaise or worsening of respiratory distress.
(d)Presence of pneumococcus in sputum confirmed with a pneumococcus kit.

Key exclusion criteria

1)History of allergy, possibly due to cephem derivatives.
2)Advanced renal dysfunction (eGFR under 30 mL/min/1.73 m2).
3)Presence of pneumonia that cannot be expected to improve by oral administrations of antibiotics.
4)Confirmed influenza virus infection. However, acute exacerbation of COPD due to secondary bacterial infections after influenza can be enrolled.
5)Presence of cystic fibrosis, active pulmonary tuberculosis or nontuberculous mycobacterial infection (including suspected).
6)Antimicrobial agents were administered within 1 week, or concomitant administration of other antimicrobial agents was necessary. However, this will not apply to patients who have been continued on low-dose, long-term macrolide therapy since before entry, as long as the dosage remains unchanged.
7)Undergoing a chronic immunosuppressive treatment using immunosuppressants.
8)A need for additional administration of oral or injectable steroids. Inhaled steroids are permitted up to 10 mg of prednisolone equivalents per day, but there should be no need for a dosage increase.
9)Complications such as a serious pulmonary malignant tumor, congestive heart failure, bronchiectasis or pneumothorax that may confound interpretation of the efficacy of the study drug.
10)Inability to administer oral antimicrobial agents (dietary nutrition is impossible).
11)Patients who are or may be pregnant, breast-feeding women and women who desire to become pregnant during the study drug administration period.
12)Any other reason that the chief investigator judges as rendering a patient inappropriate for enrollment.

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Taiga Miyazaki

Organization

Nagasaki University Hospital

Division name

Second Department of Internal Medicine

Zip code

Address

1-7-1, Sakamoto, Nagasaki city, Nagasaki prefecture.

TEL

095-819-7273

Email

taiga-m@nagasaki-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Taiga Miyazaki

Organization

Nagasaki evaluation organization for clinical interventions

Division name

office

Zip code

Address

3-2-12, Uchikanda, Chiyodaku, Tokyo

TEL

03-5297-1052

Homepage URL

Email

jimukyoku@neoci.or.jp

Institute

Nagasaki evaluation organization for clinical interventions

Institute

Department

Personal name

Organization

Nagasaki evaluation organization for clinical interventions

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

長崎大学病院（長崎県）
日本赤十字社長崎原爆病院（長崎県）
長崎みなとメディカルセンター市民病院（長崎県）
日本赤十字社長崎原爆諫早病院（長崎県）
独立行政法人地域医療機能推進機構諫早総合病院（長崎県）
地方独立行政法人佐世保市総合医療センター（長崎県）
社会医療法人財団白十字会佐世保中央病院（長崎県）
医療法人伴帥会愛野記念病院（長崎県）
独立行政法人国立病院機構嬉野医療センター（佐賀県）
千住診療所（長崎県）
医療法人栄和会　泉川病院（長崎県）
まさき内科呼吸器クリニック（長崎県）
医療法人 英尚会 中村内科（長崎県）
医療法人　松本内科医院（長崎県）
医療法人　朝長医院（佐賀県）

Date of disclosure of the study information

2013

Year

02

Month

27

Day

URL releasing protocol

https://www.jiac-j.com/article/S1341-321X(19)30082-0/fulltext

Publication of results

Published

URL related to results and publications

https://www.jiac-j.com/article/S1341-321X(19)30082-0/fulltext

Number of participants that the trial has enrolled

29

Results

Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured at test of cure, which was set at 5-10 days after treatment ceased. The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%). This study has provided positive evidence regarding the efficacy and safety of cefditoren pivoxil for the treatment of acute exacerbations of COPD.

Results date posted

2019

Year

09

Month

05

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Of the 29 patients enrolled in this study, 27 patients (93.1%) were male and most were elderly [mean (SD): 73.1 (8.1) years] with a high average smoking index [mean (SD): 1426.7 (931.7)].

Participant flow

This prospective, multicenter, single arm, interventional study was performed in 15 health care institutes from January 2013 to March 2017. We enrolled 29 patients with COPD exacerbations, of whom none met the exclusion criteria. However, six patients (20.7%) stopped their participation because of either adverse event (1 patient), concomitant disease (1 patient), or unknown reasons (4 patients).

Adverse events

During therapy, the only adverse event was pneumonia. This occurred in one patient, the severity was mild, and the condition resolved with appropriate therapy after 10 days. No serious adverse events were observed in any patient.

Outcome measures

The primary efficacy endpoint was the clinical cure rate at the test of cure. Secondary endpoints were the treatment effective rates on Day 4 and at the end of treatment, the bacteriological efficacy (bacteriological eradiation rates), and the safety outcomes.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2012

Year

11

Month

30

Day

Date of IRB

2013

Year

01

Month

20

Day

Anticipated trial start date

2013

Year

01

Month

21

Day

Last follow-up date

2017

Year

04

Month

30

Day

Date of closure to data entry

2017

Year

06

Month

30

Day

Date trial data considered complete

2017

Year

08

Month

31

Day

Date analysis concluded

2017

Year

10

Month

31

Day

Other related information

Registered date

2013

Year

02

Month

26

Day

Last modified on

2019

Year

09

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011856