Trial Outcomes & Findings for Cefiderocol Concentrations in the Lungs of Hospitalized Patients With Bacterial Pneumonia (NCT NCT03862040)

NCT ID: NCT03862040

Last Updated: 2020-11-05

Results Overview

Samples for determination of cefiderocol concentrations in the epithelial lining fluid (ELF) were collected by bronchoalveolar lavage (BAL) procedure on the inflamed section of the lung (ie, a lobe where pneumonia was expected to be present based on chest radiologic imaging) after multiple doses of cefiderocol sufficient to approximate steady state concentrations in blood. The ELF sample for the determination of cefiderocol concentrations was collected at 3 hours after the start of administration of cefiderocol for the first 4 enrolled participants and at 2 hours after the end of infusion for the following 3 participants. Cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS), with a lower limit of quantification of cefiderocol in ELF of 0.005 μg/mL. Cefiderocol concentrations in ELF were calculated using cefiderocol concentrations in BAL, adjusted by the ratio of urea concentrations in blood and BAL.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.

Results posted on

2020-11-05

Participant Flow

This study was conducted at 3 sites in the United States. Seven adults with known or suspected bacterial pneumonia being treated with standard of care (SOC) antibiotics and requiring mechanical ventilation were enrolled.

Participant milestones

Participant milestones
Measure	Cefiderocol Participants received 2 g cefiderocol (or renally adjusted doses) every 8 hours (or every 6 hours for participants with augmented renal function), administered by intravenous infusion over 3 hours for a total of 3 to 6 doses.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cefiderocol Concentrations in the Lungs of Hospitalized Patients With Bacterial Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cefiderocol n=7 Participants Participants received 2 g cefiderocol (or renally adjusted doses) every 8 hours (or every 6 hours for participants with augmented renal function), administered by intravenous infusion over 3 hours for a total of 3 to 6 doses.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.

Population: All participants who received at least 1 dose of cefiderocol and who had at least 1 evaluable concentration of cefiderocol in bronchoalveolar lavage fluid.

Outcome measures

Outcome measures
Measure	Cefiderocol n=7 Participants Participants received 2 g cefiderocol (or renally adjusted doses) every 8 hours (or every 6 hours for participants with augmented renal function), administered by intravenous infusion over 3 hours for a total of 3 to 6 doses.
Concentration of Cefiderocol in Epithelial Lining Fluid 3 hours after start of infusion	7.63 μg/mL Interval 3.1 to 20.7
Concentration of Cefiderocol in Epithelial Lining Fluid 2 hours after end of infusion	10.4 μg/mL Interval 7.19 to 15.9

PRIMARY outcome

Timeframe: At the third dosing (or sixth dosing for participants with severe renal impairment; 16 or 40 hours after start of the first dose, respectively), at 3 hours after the start of the infusion or 2 hours after the end of infusion.

Population: All participants who received at least 1 dose of cefiderocol and who had at least 1 evaluable concentration of cefiderocol in bronchoalveolar lavage fluid. Cefiderocol concentration was measured 3 hours after the start of the infusion in the first 4 enrolled participants and 2 hours after the end of infusion in the following 3 participants.

The concentration of cefiderocol in ELF to plasma ratio (RC,E/P) represents the penetration of cefiderocol into infected lung tissue. ELF and plasma cefiderocol concentrations were determined using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The lower limit of quantification of cefiderocol in plasma and ELF was 0.1 μg/mL and 0.005 μg/mL, respectively.

Outcome measures

Outcome measures
Measure	Cefiderocol n=7 Participants Participants received 2 g cefiderocol (or renally adjusted doses) every 8 hours (or every 6 hours for participants with augmented renal function), administered by intravenous infusion over 3 hours for a total of 3 to 6 doses.
Ratio of the Concentration of Cefiderocol in Epithelial Lining Fluid Relative to Plasma 3 hours after start of infusion	0.0893 ratio Interval 0.0379 to 0.178
Ratio of the Concentration of Cefiderocol in Epithelial Lining Fluid Relative to Plasma 2 hours after end of infusion	0.231 ratio Interval 0.187 to 0.347

Adverse Events

Cefiderocol

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cefiderocol n=7 participants at risk Participants received 2 g cefiderocol (or renally adjusted doses) every 8 hours (or every 6 hours for participants with augmented renal function), administered by intravenous infusion over 3 hours for a total of 3 to 6 doses.
Respiratory, thoracic and mediastinal disorders Wheezing	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Blood and lymphatic system disorders Anaemia	28.6% 2/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Blood and lymphatic system disorders Thrombocytopenia	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Cardiac disorders Atrial fibrillation	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Injury, poisoning and procedural complications Contusion	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Injury, poisoning and procedural complications Tracheostomy malfunction	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Metabolism and nutrition disorders Hypokalaemia	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Metabolism and nutrition disorders Hypernatraemia	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Metabolism and nutrition disorders Hypophosphataemia	28.6% 2/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Metabolism and nutrition disorders Hyperchloraemia	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Renal and urinary disorders Renal failure	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Renal and urinary disorders Acute kidney injury	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Infections and infestations Bacteriuria	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Investigations Blood urea increased	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
Injury, poisoning and procedural complications Wound dehiscence/	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.
General disorders Implant site dehiscence	14.3% 1/7 • From the start of the first infusion of cefiderocol up to 7 days after last dose, up to 9 days.

Additional Information

Shionogi Clinical Trials Administrator

Shionogi Inc.

Phone: 800-849-9707

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Publication restrictions are in place

Restriction type: OTHER