Trial Outcomes & Findings for Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli (OVERCOME) (NCT NCT01597973)

Last Updated: 2022-11-14

Results Overview

Determine whether the treatment regimen of colistin combined with a carbapenem (imipenem or meropenem) is associated with a decreased risk for all-cause mortality during the 30 day post-enrollment period compared to colistin combined with a placebo for subjects with bloodstream infection (BSI) and/or pneumonia due to extensively drug-resistant Gram-negative bacilli (XDR-GNB).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

467 participants

Primary outcome timeframe

participants will be followed daily for the duration of hospital stay, an expected average of 4 weeks

Results posted on

2022-11-14

Participant Flow

While 467 participants completed an informed consent document, 3 were deemed ineligible

Participant milestones

Participant milestones
Measure	Colistin and Placebo colistin and placebo: colistin- loading dose standard, maintenance dosed based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Overall Study STARTED	234	230
Overall Study Began First Dose	230	228
Overall Study COMPLETED	214	211
Overall Study NOT COMPLETED	20	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Colistin and Placebo colistin and placebo: colistin- loading dose standard, maintenance dosed based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Overall Study Found ineligible before study medication started	4	2
Overall Study Eligible pathogen not confirmed	14	15
Overall Study LAR not authorized to consent	0	1
Overall Study Ineligible due to early seizures	1	0
Overall Study Ineligible due to non-target infection	1	1

Baseline Characteristics

Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli (OVERCOME)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Colistin and Placebo n=234 Participants colistin and placebo: colistin- loading dose standard, maintenance dosed based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=230 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function	Total n=464 Participants Total of all reporting groups
Age, Continuous	68.0 years STANDARD_DEVIATION 16.3 • n=5 Participants	68.4 years STANDARD_DEVIATION 15.4 • n=7 Participants	68.2 years STANDARD_DEVIATION 15.9 • n=5 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	84 Participants n=7 Participants	174 Participants n=5 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	146 Participants n=7 Participants	290 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	96 Participants n=5 Participants	91 Participants n=7 Participants	187 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	116 Participants n=5 Participants	120 Participants n=7 Participants	236 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Greece	14 participants n=5 Participants	15 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	23 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Taiwan	29 participants n=5 Participants	28 participants n=7 Participants	57 participants n=5 Participants
Region of Enrollment Italy	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Israel	89 participants n=5 Participants	93 participants n=7 Participants	182 participants n=5 Participants
Region of Enrollment Thailand	68 participants n=5 Participants	64 participants n=7 Participants	132 participants n=5 Participants
Region of Enrollment Bulgaria	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants

PRIMARY outcome

Timeframe: participants will be followed daily for the duration of hospital stay, an expected average of 4 weeks

Outcome measures

Outcome measures
Measure	Colistin and Placebo n=214 Participants colistin and placebo: colistin- loading dose standard, maintenance dose based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=211 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Mortality Dead	92 Participants	78 Participants
Mortality Alive	122 Participants	133 Participants

SECONDARY outcome

Timeframe: patients' resistance data will be collected up to 30 days

Population: Follow up cultures were unable to be obtained for some subjects. Therefore emergence of resistance status for those subjects could not be determined.

Determine what treatment regimen (colistin monotherapy (combined with placebo)) or colistin combined a carbapenem (imipenem or meropenem) is more likely to reduce the frequency of emergence of colistin resistance among XDR-GNB isolates during therapy. Measurements of Minimum Inhibitory Concentration of colistin to XDR-GNB. This is shown below as numbers of those subjects who develop colistin resistance and their percentages of the total completed population.

Outcome measures

Outcome measures
Measure	Colistin and Placebo n=173 Participants colistin and placebo: colistin- loading dose standard, maintenance dose based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=173 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Number of Participants Who Develop Colistin Resistance	18 Participants	15 Participants

SECONDARY outcome

Timeframe: 48 hours after end of treatment, that is up to 16 days

Population: 54 patients were omitted due to death before 48 hours (n=40) or incomplete PaO2/FiO2 data (n=14).

Clinical failure as defined by either Blood Stream Infection (BSI) or Pneumonia; based on death between 48 hours and end of treatment, medication change from protocol, a positive blood culture after 5 days of blood stream infection treatment, or no improvements in PaO2/FiO2 at end of treatment.

Outcome measures

Outcome measures
Measure	Colistin and Placebo n=186 Participants colistin and placebo: colistin- loading dose standard, maintenance dose based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=185 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Clinical Failure at the End of Therapy	115 Participants	97 Participants

SECONDARY outcome

Timeframe: From 5 days after enrollment up to 14 days following enrollment (i.e. end of treatment)

Population: Some patients did not have data in the time window of interest (from 5 days following enrollment until end of treatment, 14 days) (e.g. from some specimens not being produced or available).

Microbiologic cure at the end of therapy as defined by the number of participants who no longer have the causative XDR-GNB pathogens for their BSI or pneumonia identified based on microbiologic testing

Outcome measures

Outcome measures
Measure	Colistin and Placebo n=169 Participants colistin and placebo: colistin- loading dose standard, maintenance dose based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=174 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Microbiologic Cure at the End of Therapy Cure	112 Participants	105 Participants
Microbiologic Cure at the End of Therapy Failure	57 Participants	69 Participants

SECONDARY outcome

Timeframe: Up to 16 days

Population: Follow up creatinine clearance data was missing from many patients resulting in a smaller analysis population for nephrotoxicity.

Frequency is shown for each of the following: Nephrotoxicity, Hepatotoxicity, Seizures, Neurotoxicity, Hypersensitivity reaction

Outcome measures

Outcome measures
Measure	Colistin and Placebo n=214 Participants colistin and placebo: colistin- loading dose standard, maintenance dose based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=211 Participants colistin and a carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Number of Participants With Toxicities Related to Treatment Medications Nephrotoxicity	88 Participants	85 Participants
Number of Participants With Toxicities Related to Treatment Medications Hypersensitivity reaction	3 Participants	7 Participants
Number of Participants With Toxicities Related to Treatment Medications Hepatotoxicity	32 Participants	31 Participants
Number of Participants With Toxicities Related to Treatment Medications Seizures	4 Participants	3 Participants
Number of Participants With Toxicities Related to Treatment Medications Neurotoxicity	11 Participants	5 Participants

Adverse Events

Colistin and Placebo

Serious events: 13 serious events

Other events: 169 other events

Deaths: 98 deaths

Colistin and a Carbapenem

Serious events: 10 serious events

Other events: 161 other events

Deaths: 85 deaths

Serious adverse events

Other adverse events

Additional Information

Jolene Daniel

University of Michigan

Phone: 732 235-7713

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Colistin and Placebo n=230 participants at risk colistin and placebo: colistin- loading dose standard, maintenance dosed based on patient's renal function placebo- mimic meropenem (blinded)	Colistin and a Carbapenem n=228 participants at risk colistin and carbapenem: colistin standard loading dose, maintenance dose based on patient's renal function carbapenem- dose based on patient's renal function
Infections and infestations Abdominal infection	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Cardiac disorders Acute coronary syndrome	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Renal and urinary disorders Acute kidney injury	1.3% 3/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	1.8% 4/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Investigations Blood bilirubin increased	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Cardiac disorders Cardiac arrest	0.87% 2/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Investigations Cardiac troponin I increased	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Nervous system disorders Depressed level of consciousness	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Gastrointestinal disorders Gastric hemorrhage	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Metabolism and nutrition disorders Hyperphosphatemia	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Metabolism and nutrition disorders Hypoglycemia	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Metabolism and nutrition disorders Hypophosphatemia	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Vascular disorders Hypotension	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Gastrointestinal disorders Intestinal ischemia	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Gastrointestinal disorders Intra-abdominal hemorrhage	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Infections and infestations Lung infection	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progression of pre-existing cancer	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.87% 2/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Nervous system disorders Seizure	1.3% 3/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Infections and infestations Sepsis	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Infections and infestations Skin infection	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Infections and infestations Splenic abscess	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.44% 1/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.
Nervous system disorders Stroke	0.43% 1/230 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.	0.00% 0/228 • For AEs, the assessment period begins at the time of enrollment and continues until 48 hours after end of treatment, that is up to 16 days. (as 48 hours is total removal of colistin from the patient has occurred). All-Cause Mortality, the Primary Objective is assessed up to 30 days after enrollment.