Clinical Trial Results:
Perioperative complications in obese and non-obese patients: Prevention and treatment of wound infections and post-operative pain. Prospective, open, monocentric study to investigate perioperative tissue concentrations of antibiotics and regional analgesics using microdialysis in obese and non-obese patients.

Trial information Top of page
Trial identification
Sponsor protocol code	Mikrodialyse
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	University of Leipzig
Sponsor organisation address	Ritterstr. 26, Leipzig, Germany,
Public contact	Clinical Trial Centre Leipzig, ZKS Leipzig - KKS, 0049 034116 254,
Scientific contact	Clinical Trial Centre Leipzig, ZKS Leipzig - KKS, 0049 034116 254,
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	13 Sep 2019
Is this the analysis of the primary completion data?	Yes
Primary completion date	21 Mar 2017
Global end of trial reached?	Yes
Global end of trial date	21 Mar 2017
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The establishment of an optimized drug-dose-model based on tissue concentrations of antibiotics, analgesics and other substances in obese patients.
Protection of trial subjects	The trial did not contain an intervention or subject the patients to additional risk.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	28 Oct 2013
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Germany: 125
Worldwide total number of subjects	125
EEA total number of subjects	125
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	117
From 65 to 84 years	8
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Obese patients fulfilling the inclusion/exclusion criteria were all asked to participate. Matched non-obese patients were identified vial the electronic medical records and asked to participate.
Pre-assignment period milestones
Number of subjects started	125
Number of subjects completed	125
Period 1
Period 1 title	Baseline (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	Obese
Arm description	Patients with BMI >= 35 kg/m^2
Arm type	Experimental
Investigational medicinal product name	Linezolid
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	600 mg, single dose
Investigational medicinal product name	Meropenem
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single dose
Investigational medicinal product name	paracetamol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single use
Investigational medicinal product name	metamizol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single dose
Investigational medicinal product name	tigecyclin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	100 mg, single dose
Investigational medicinal product name	Cefazolin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	2000 mg, single dose
Investigational medicinal product name	metronidazol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	500 mg, single dose
Investigational medicinal product name	fosfomycin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	8000 mg, single dose
Investigational medicinal product name	piperacillin/tazobactam
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	4000 mg (piperacillin) / 500 mg (tazobactam), single dose
Arm title	Non-obese
Arm description	Patients with 18.5 <= BMI < 30 kg/m^2
Arm type	Experimental
Investigational medicinal product name	Linezolid
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	600 mg, single dose
Investigational medicinal product name	Meropenem
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single dose
Investigational medicinal product name	paracetamol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single use
Investigational medicinal product name	metamizol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	1000 mg, single dose
Investigational medicinal product name	tigecyclin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	100 mg, single dose
Investigational medicinal product name	Cefazolin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	2000 mg, single dose
Investigational medicinal product name	metronidazol
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	500 mg, single dose
Investigational medicinal product name	fosfomycin
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	8000 mg, single dose
Investigational medicinal product name	piperacillin/tazobactam
Investigational medicinal product code
Other name
Pharmaceutical forms	Infusion
Routes of administration	Intravenous use
Dosage and administration details	4000 mg (piperacillin) / 500 mg (tazobactam), single dose
Number of subjects in period 1 Obese Non-obese Started 65 60 Completed 65 60

Subject disposition Top of page

Baseline characteristics Top of page

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Obese
Reporting group description	Patients with BMI >= 35 kg/m^2
Reporting group title	Non-obese
Reporting group description	Patients with 18.5 <= BMI < 30 kg/m^2

End points Top of page

Primary: Area under the time-concentration curve in ISF Top of page
End point title	Area under the time-concentration curve in ISF
End point description
End point type	Primary
End point timeframe	0-8 hours after administration
End point values Obese Non-obese Number of subjects analysed 13 [1] 14 [2] Units: mg/l*h     log mean (standard deviation) 1052 ( 394 ) 1929 ( 725 )
Notes [1] - 15 obese patients received fosfomycin, 2 did not provide valid data in the ISF [2] - 14 non-obese patients received fosfomycin, 1 did not provide valid data in the ISF
Statistical analysis title	Comparison of AUC between obese and non-obese
Statistical analysis description	The linear-up/log-down trapezoidal rule was used for calculation of AUC. Extrapolation to infinity was based on the last predicted concentration. Comparison between the groups used a t-test with Welsh correction.
Comparison groups	Obese v Non-obese
Number of subjects included in analysis	27
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.001
Method	t-test, 2-sided
Parameter type	Mean difference (final values)
Point estimate	877
Confidence interval
level	95%
sides	2-sided
lower limit	414
upper limit	1340

Primary: Area under the time-concentration curve in ISF Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Per Patient: From the administration of the study drug until 72 hours later
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	20.1
Reporting groups
Reporting group title	Obese
Reporting group description	Patients with BMI >= 35 kg/m^2
Reporting group title	Non-obese
Reporting group description	Patients with 18.5 <= BMI < 30 kg/m^2
Serious adverse events Obese Non-obese Total subjects affected by serious adverse events      subjects affected / exposed 4 / 65 (6.15%) 2 / 60 (3.33%)      number of deaths (all causes) 1 0      number of deaths resulting from adverse events 1 0 Investigations Transaminases increased      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Injury, poisoning and procedural complications Anastomotic leak      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Cardiac disorders Cardiac arrest      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Gastrointestinal disorders Gastrointestinal haemorrhage      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations Pneumonia      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Septic shock      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events Obese Non-obese Total subjects affected by non serious adverse events      subjects affected / exposed 40 / 65 (61.54%) 44 / 60 (73.33%) Investigations Mean arterial pressure decreased      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0 Transaminases increased      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0 C-reactive protein increased      subjects affected / exposed 0 / 65 (0.00%) 2 / 60 (3.33%)      occurrences all number 0 2 Inflammatory marker increased      subjects affected / exposed 0 / 65 (0.00%) 2 / 60 (3.33%)      occurrences all number 0 2 Injury, poisoning and procedural complications Anastomotic leak      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0 Procedural hypotension      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0 Vascular disorders Hypotension      subjects affected / exposed 37 / 65 (56.92%) 40 / 60 (66.67%)      occurrences all number 37 40 Cardiac disorders Cardiac arrest      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Cardiac disorder      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Sinus bradycardia      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Gastrointestinal disorders Gastrointestinal haemorrhage      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0 Respiratory, thoracic and mediastinal disorders Hypercapnia      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Hypocapnia      subjects affected / exposed 1 / 65 (1.54%) 1 / 60 (1.67%)      occurrences all number 1 1 Pleural effusion      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Renal and urinary disorders Acute kidney injury      subjects affected / exposed 0 / 65 (0.00%) 1 / 60 (1.67%)      occurrences all number 0 1 Infections and infestations Urinary tract infection      subjects affected / exposed 0 / 65 (0.00%) 2 / 60 (3.33%)      occurrences all number 0 2 Pneumonia      subjects affected / exposed 1 / 65 (1.54%) 1 / 60 (1.67%)      occurrences all number 1 1 Septic shock      subjects affected / exposed 1 / 65 (1.54%) 0 / 60 (0.00%)      occurrences all number 1 0

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
20 Nov 2014	New substances were included for investigation (Fosfomycin, Piperacilin/ Tazobactam) in 30 additional patients
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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