Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006423

Trial Description

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Title

Quantification of Drugs and Their Metabolites in Patients at the Cologne University Hospital

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The study includes two study parts in which blood is collected from the patients.

Study part A (observational study, already received positive ethics committee vote; Our
sign: 12-330): Use of blood samples gathered during routine blood withdrawal Study part B
(interventional study in the sense of additional blood samples but without an
investigational product): Optional, for further pharmacokinetic questions: blood withdrawal
with a maximum of 20 ml ( ten tubes of 2 ml each) within a maximal study length of four
weeks.

The primary objective of this study is to gain an overview about drug concentrations in
plasma and/or cerebrospinal fluid (CSF), in order to determine pharmacokinetics of drugs in
patients. Any drug may be tested, however the initial focus is on antiinfective,
antineoplastic, and antipsychotic drugs.

Many published studies show that there is a profound lack of information on pharmacokinetics
and interactions of many commonly used drugs in clinical routine, and that drug
concentrations, if controlled by therapeutic drug monitoring, are not in the therapeutic
range (provided that such ranges are known at all).

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Brief Summary in Scientific Language

For an effective pharmacotherapy in patients with different demographic characteristics
(age, weight or lean body mass), there is often a lack of information on the dosage of
drugs.

The predictability of the action of a drug is additionally impaired by genetic
predisposition. Even if the effect of genetic variants has been demonstrated, the respective
characteristic for the patient is usually not known.

For example, a study (Gamelin et al., 2008) of the "old" cytostatic drug 5-fluorouracil
shows its genetically-dependent efficacy.

Only in about one third of patients does the concentration reach the desired therapeutic
range (the dosage adjusted to body surface).

There is a significant lack of information on the pharmacokinetics, especially in critically
ill patients.

These patients are excluded in modern drug approval studies, although it is anticipated
that, depending on the drug, many patients with severely impaired renal function, renal
replacement therapy, severe hepatic dysfunction, sepsis or multiple organ failure may later
on obtain the substance.

This knowledge gap on the specific pharmacokinetics of drugs in selected populations is
present not only for new drugs, but also for those that have already been used in therapy
for decades.

Particularly for the effect of body weight and liver function on pharmacokinetics, data is
very sparse. For the latter, the lack of data is particularly striking, when searching for
data concerning patients with severe hepatic dysfunction. If occasional data for specific
drugs are available, then for most substances these are not sufficient to develop a safe
dosing regimen, e.g. for the aforementioned example of 5-fluorouracil. Furthermore, for many
drugs reliable pharmacokinetic data in renal impairment or renal replacement therapy are not
available. The available data is generally much better than in hepatic insufficiency, but
especially the lack of data on the pharmacokinetics of metabolites in renal insufficiency
may be of relevance, as such metabolites are active and play an important role for the
effect, but they may also be responsible for side effects. To illustrate, the
"Fachinformation" (as of April 30th 2012), the legally binding document for dosing issues of
drugs in Germany, is attached. This table provides a selection of important drugs, while it
is not exhaustive.

In hospitals predominantly severely ill patients are treated and several drugs are
administered simultaneously. Thus, the issue of drug-drug interaction is in the center of
attention. Unexpected new clinical interactions of drugs known for a long time, or
interactions of well-known substances with new substances are reported. A recent example is
an interaction caused by Cotrimoxazol, a drug combination used for decades (Antoniou et al.,
2011).

In summary, it can be stated that in drug therapy there is a high demand for both the
quantification of in vivo plasma and liquor drug concentrations and quantifying the effect
of different characteristics on the pharmacokinetics of the drugs. Thus, concentrations for
a broad range of substances which are used in the Cologne University Hospital should be
measured, including their respective metabolites. Concentrations both in plasma and in CSF
(for drugs supposed to have an effect on the central nervous system) will be quantified.
This screening approach is possible due to the increasing availability of highly sensitive
and selective liquid chromatography - tandem mass spectrometry (LC-MS/MS) methods, thereby
the number of measurable substances markedly increased. The initial focus of our project is
on the antiinfective, antineoplastic and antipsychotic agents.

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Organizational Data

  •   DRKS00006423
  •   2014/11/21
  •   2013/03/14
  •   yes
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Secondary IDs

  •   2013-000779-33 
  •   NCT01828372  (ClinicalTrials.gov)
  •   KPUK-12-GenPOPPK-2  (University of Cologne)
  •   2013-000779-33 
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Health Condition or Problem studied

  •   Liver Insufficiency
  •   Kidney Failure, Chronic
  •   Obesity
  •   Pregnancy
  •   Breast Feeding, Exclusive
  •   Sepsis
  •   Multiple Organ Failure
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Interventions/Observational Groups

  •   Other: additional blood withdrawals
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Screening
  •   Single (group)
  •   N/A
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Primary Outcome

- Pharmacokinetic Outcome Measures (e.g., Cmax, AUC); time frame: within four weeks after administration of drug of interest; These assessments rely on multiple measurements over time and the Time Frame may include multiple time points describing the interval at which data are collected

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Secondary Outcome

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   2013/05/31
  •   1000
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Both genders are included.

- Patients willing and capable to confirm written consent prior to enrolment after
ample information was given are eligible for the study.

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Exclusion Criteria

- In Study Part B patients with hemoglobin less 7 mg/dl or less 10 mg/dl including
serious symptoms of anemia such as increased heart rate, shortness of breath,
dizziness, weakness etc.

- The hemoglobin value must not be 10 days or older.

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Addresses

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    • University of Cologne
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    • Department of Pharmacology
    • Uwe Fuhr, Professor 
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    • Uwe Fuhr, Professor 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/07/16
* This entry means the parameter is not applicable or has not been set.