Trial Outcomes & Findings for IV Colistin for Pulmonary Exacerbations: Improving Safety and Efficacy (NCT NCT02918409)
NCT ID: NCT02918409
Last Updated: 2023-04-21
Results Overview
absolute change in forced expiratory volume at one second (FEV1) % predicted, or percent predicted FEV1, between study arms with acute pulmonary exacerbation (APE) treatment
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
51 participants
Primary outcome timeframe
up to 14 days, from beginning to end of APE treatment
Results posted on
2023-04-21
Participant Flow
Participant milestones
| Measure |
Standard Colistin Arm
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Overall Study
STARTED
|
16
|
10
|
25
|
|
Overall Study
COMPLETED
|
15
|
10
|
24
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Standard Colistin Arm
n=15 Participants
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 Participants
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 Participants
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=15 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=49 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=15 Participants
|
10 Participants
n=10 Participants
|
24 Participants
n=24 Participants
|
49 Participants
n=49 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=15 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=49 Participants
|
|
Age, Continuous
|
30 years
STANDARD_DEVIATION 10.6 • n=15 Participants
|
33 years
STANDARD_DEVIATION 12.3 • n=10 Participants
|
31 years
STANDARD_DEVIATION 7.2 • n=24 Participants
|
31 years
STANDARD_DEVIATION 9.3 • n=49 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=15 Participants
|
7 Participants
n=10 Participants
|
12 Participants
n=24 Participants
|
31 Participants
n=49 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=15 Participants
|
3 Participants
n=10 Participants
|
12 Participants
n=24 Participants
|
18 Participants
n=49 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
15 participants
n=15 Participants
|
10 participants
n=10 Participants
|
24 participants
n=24 Participants
|
49 participants
n=49 Participants
|
PRIMARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentabsolute change in forced expiratory volume at one second (FEV1) % predicted, or percent predicted FEV1, between study arms with acute pulmonary exacerbation (APE) treatment
Outcome measures
| Measure |
Standard Colistin Arm
n=15 Participants
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 Participants
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 Participants
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Absolute Change in Forced Expiratory Volume at One Second (FEV1) % Predicted Between Study Arms With Acute Pulmonary Exacerbation (APE) Treatment
|
6.5 ppFEV1
Standard Deviation 9.5
|
4.4 ppFEV1
Standard Deviation 3.0
|
4.5 ppFEV1
Standard Deviation 6.3
|
PRIMARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
| Measure |
Standard Colistin Arm
n=15 Participants
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 Participants
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 Participants
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Rate of Occurrence of the Development of Acute Kidney Injury (AKI) During APE Treatment
|
1 Participants
|
0 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: from the beginning of APE treatment to 12 months after APE treatmenttime to next admission for exacerbation measured in days when comparing of different antibiotic therapies
Outcome measures
| Measure |
Standard Colistin Arm
n=15 Participants
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 Participants
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 Participants
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Longitudinal Differences in Exacerbation Rates Between Tobramycin and Colistin Use as Seen in Readmission Rate
|
154 days
Standard Deviation 115
|
283 days
Standard Deviation 309
|
241 days
Standard Deviation 184
|
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentabsolute occurrences of adverse event rates are being compared between treatment groups using logistic regression, adjusting for age, co-administration of medications such as vancomycin and trimethoprim-sulfamethoxazole, baseline FEV1, admits in the previous year, and diagnosis of CF related diabetes (CFRD) as covariates.
Outcome measures
| Measure |
Standard Colistin Arm
n=15 Participants
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 Participants
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 Participants
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Differences in Occurrences of Neurotoxicity and Ototoxicity Related Side Effects Between Study Arms as Reported by Treating Physician(s)
|
2 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 14 days, from beginning to end of APE treatmentOutcome measures
Outcome data not reported
Adverse Events
Standard Colistin Arm
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Modified Colistin Arm
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Standard Tobramycin Arm
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Standard Colistin Arm
n=15 participants at risk
Subjects initially receive IV colistin 2.5 mg/kg/d divided into three times daily (TID) dosing. Subjects receiving colistin will undergo a 2 day up-titration of dose to an ultimate dose of 4-5 mg/kg/day, for a total treatment of 14 days. The drug is infused over 30 minutes on a TID dosing schedule.
Colistin
|
Modified Colistin Arm
n=10 participants at risk
Subjects receiving IV colistin undergo a 2 day up-titration to a maximum dose of 5 mg/kg/day, divided into twice daily (BID) dosing, for a total treatment of 14 days. The drug is infused over 30 minutes BID. Steady state plasma concentrations on day 3 of therapy (on 2nd- 3rd dose once at goal dosing) will be measured; specifically, colistin peak (30 minutes after infusion), midpoint (6 hour) and trough (30 minutes prior to next infusion).
Colistin
|
Standard Tobramycin Arm
n=24 participants at risk
Subjects receive IV tobramycin 8-10 mg/kg/day with once daily dosing for 14 days. Peaks and troughs are drawn with the second dose of tobramycin, and the drug is infused over 30 minutes
Tobramycin
|
|---|---|---|---|
|
Ear and labyrinth disorders
Oto- or vestibular toxicity
|
0.00%
0/15 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
0.00%
0/10 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
4.2%
1/24 • Number of events 1 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
|
Renal and urinary disorders
Renal toxicity
|
6.7%
1/15 • Number of events 1 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
0.00%
0/10 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
25.0%
6/24 • Number of events 6 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
|
General disorders
Oral paresthesias
|
26.7%
4/15 • Number of events 4 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
10.0%
1/10 • Number of events 1 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
0.00%
0/24 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
|
General disorders
Headache
|
13.3%
2/15 • Number of events 2 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
10.0%
1/10 • Number of events 1 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
0.00%
0/24 • 14 days
The total number of participants at risk in each arm of the study represents the number enrolled in each arm of the study, not the total number enrolled. The study arms were not enrolled equally.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place