Combined Administration of Nebulized Amikacin in Patients With Acute Exacerbation of Non-Cystic Fibrosis Bronchiectasis

• Sponsor: Qilu Hospital of Shandong University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02081963
• Collaborator: (none)
• Enrollment: 178
• Location: 1
• Arms: 2
• Actual Duration (Months): 33.1
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

This is a multi-centered, randomized, controlled study to assess the efficacy, indications and adverse reactions of combined administration of nebulized amikacin in patients with acute exacerbation of non-cystic fibrosis bronchiectasis and to evaluate whether inhaled antibiotics are more likely to cause bacterial resistance.

Condition or Disease	Intervention/Treatment	Phase
Non-Cystic Fibrosis Bronchiectasis	Drug: Amikacin; Drug: Normal saline	Phase 4

Detailed Description

Objective: To assess the efficacy, indications and adverse reactions of combined administration of nebulized amikacin in patients with acute exacerbation of non-cystic fibrosis bronchiectasis and to evaluate whether inhaled antibiotics are more likely to cause bacterial resistance.

Methods: Patients with acute exacerbation of non-cystic fibrosis bronchiectasis will be randomly assigned to the observer group (participants receive nebulized amikacin BID for 14 days in combination with standard treatment) or the control group (participants receive nebulized 0.9% saline BID for 14 days in combination with standard treatment). The primary endpoint was bacterial clearance rate of sputum.

Expected results: Compared with the control group, bacterial clearance rate of sputum of the observer Group will increase significantly.

Study Design

• Study Type: Interventional
• Actual Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled Study of Combined Administration of Nebulized Amikacin in Patients With Acute Exacerbation of Non-Cystic Fibrosis Bronchiectasis
• Actual Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nebulized amikacin Participants receive nebulized amikacin BID for 14 days in combination with standard treatment.	Drug: Amikacin; Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.
Other: Nebulized normal saline Participants received nebulized normal saline BID for 14 days in combination with standard treatment.	Drug: Normal saline; Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.

Outcome Measures

Primary Outcome Measures

1. Bacterial Clearance Rate of Sputum [after 14 days]

   The bacterial eradication rate of the sputum was calculated by the number of P. aeruginosa-eradicated cases according to sputum culture testing result. Sputum samples were collected in the morning after toothbrushing and gargling, before the patients used any medicine. Eligible sputum samples were defined as having ≥25 white blood cells/highpower field and ≤10 epithelial cells/high-power field; the samples were sent for testing within 60 min. Sputum samples were collected again after 14 days. If the second sputum culture test showed a negative result after the first one had been positive, it was defined as eradicated.

Secondary Outcome Measures

1. Total Sputum Weight (Collected Over 24 h) After 14 Days of Treatment [after 14 days]

2. Sputum Property Score After 14 Days of Treatment [after 14 days]

   The sputum properties were graded from 1 to 4, with 1 being assigned to transparent mucous sputum, 2 to yellow purulent sputum, 3 to green purulent sputum, and 4 to black green purulent sputum. Higher scores mean a worse outcome.

3. Forced Expiratory Volume in One Second (FEV1) (Percent of Predicted for Age) After 14 Days of Treatment [after 14 days]

4. Forced Expiratory Volume in One Second (FEV1) After 14 Days of Treatment [after 14 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female study subjects ≥18 years of age and ≤80 years of age;

• Confirmed diagnosis of idiopathic bronchiectasis or postinfectious bronchiectasis;

• Confirmation of infection with Pseudomonas aeruginosa at screening;

• Are sensitive to amikacin;

• Acute exacerbation of bronchiectasis.

Exclusion Criteria:

• Bronchiectasis due to special causes;

• Smokers;

• Are associated with bronchial asthma;

• Have any serious or active medical or psychiatric illness;

• Be allergic to amikacin or not tolerant to nebulised amikacin(FEV1 reduces ≥15% after inhaling amikacin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Qilu Hospital of Shandong University	Jinan	Shandong	China	250012

Sponsors and Collaborators

• Qilu Hospital of Shandong University

Investigators

• Study Director: Yu Li, Professor, Director

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Qian Qi, assistant director, Qilu Hospital of Shandong University
• ClinicalTrials.gov Identifier: NCT02081963
• Other Study ID Numbers: NCFB-AMK-01
• First Posted: Mar 7, 2014
• Last Update Posted: Apr 24, 2019
• Last Verified: Nov 1, 2015

• Keywords provided by Qian Qi, assistant director, Qilu Hospital of Shandong University: Nebulized amikacin;; Non-Cystic Fibrosis Bronchiectasis;; Bacterial clearance rate of sputum；; Acute exacerbation.
• Additional relevant MeSH terms: Bronchiectasis; Fibrosis; Amikacin

Study Results

Participant Flow

Recruitment Details	Eligible patients were screened and randomized at five tertiary hospitals in Shandong Province, China.
Pre-assignment Detail	A total of 178 patients were screened in this study, and 26 unquali-fied patients (14.6%) were excluded.

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Period Title: Overall Study
STARTED	79	73
COMPLETED	74	69
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline	Total
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.	Total of all reporting groups
Overall Participants	79	73	152
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	70 88.6%	67 91.8%	137 90.1%
>=65 years	9 11.4%	6 8.2%	15 9.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (13.0)	56.5 (10.8)	56.9 (11.8)
Sex: Female, Male (Count of Participants)
Female	46 58.2%	37 50.7%	83 54.6%
Male	28 35.4%	32 43.8%	60 39.5%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
China	74 93.7%	69 94.5%	143 94.1%

Outcome Measures

1. Primary Outcome

Title	Bacterial Clearance Rate of Sputum
Description	The bacterial eradication rate of the sputum was calculated by the number of P. aeruginosa-eradicated cases according to sputum culture testing result. Sputum samples were collected in the morning after toothbrushing and gargling, before the patients used any medicine. Eligible sputum samples were defined as having ≥25 white blood cells/highpower field and ≤10 epithelial cells/high-power field; the samples were sent for testing within 60 min. Sputum samples were collected again after 14 days. If the second sputum culture test showed a negative result after the first one had been positive, it was defined as eradicated.
Time Frame	after 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Measure Participants	74	69
Count of Participants [Participants]	38 48.1%	16 21.9%

2. Secondary Outcome

Title	Total Sputum Weight (Collected Over 24 h) After 14 Days of Treatment
Time Frame	after 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Measure Participants	74	69
Mean (Standard Deviation) [g]	18.4 (20.2)	16.5 (20.8)

3. Secondary Outcome

Title	Sputum Property Score After 14 Days of Treatment
Description	The sputum properties were graded from 1 to 4, with 1 being assigned to transparent mucous sputum, 2 to yellow purulent sputum, 3 to green purulent sputum, and 4 to black green purulent sputum. Higher scores mean a worse outcome.
Time Frame	after 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Measure Participants	74	69
Mean (Standard Deviation) [score on a scale]	1.3 (0.6)	1.3 (0.6)

4. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) (Percent of Predicted for Age) After 14 Days of Treatment
Time Frame	after 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Measure Participants	74	69
Mean (Standard Deviation) [Percent of Predicted]	56.9 (23.9)	60.0 (25.3)

5. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) After 14 Days of Treatment
Time Frame	after 14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebulized Amikacin	Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.	Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
Measure Participants	74	69
Mean (Standard Deviation) [L]	1.3 (0.7)	1.5 (0.7)

Adverse Events

Arm/Group Title	Nebulized Amikacin		Nebulized Normal Saline
Arm/Group Description	Participants receive nebulized amikacin BID for 14 days in combination with standard treatment. Amikacin: Nebulized 0.2g of amikacin and 2 mL of normal saline twice a day for 14 days in combination with standard treatment.		Participants received nebulized normal saline BID for 14 days in combination with standard treatment. Normal saline: Nebulized 3 mL of normal saline twice a day for 14 days in combination with standard treatment.
All Cause Mortality
	Nebulized Amikacin		Nebulized Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/79 (1.3%)		1/73 (1.4%)
Serious Adverse Events
	Nebulized Amikacin		Nebulized Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/79 (3.8%)		1/73 (1.4%)
Gastrointestinal disorders
nausea	1/79 (1.3%)		0/73 (0%)
Respiratory, thoracic and mediastinal disorders
bronchospasms	2/79 (2.5%)		1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	Nebulized Amikacin		Nebulized Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/79 (1.3%)		1/73 (1.4%)
Gastrointestinal disorders
nausea	1/79 (1.3%)		1/73 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.