Trial document




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  DRKS00006556

Trial Description

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Title

Prospective observational study to optimize and simplify the diagnosis of pathologically increased intra-abdominal pressure in critically ill children

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Trial Acronym

pedACS concept study

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Many diseases - which cause an intensive care unit stay - lead to the development of organ and tissue swelling or fluid retention in the abdominal or thoracic cavity. Since the space in the abdomen is limited (especially in children), these processes may increase the pressure within the abdominal cavity, which can restrict blood flow to abdominal organs and thus impede their oxygen supply. As a consequence, organs may fall ill, which initially may not have led to the intensive care unit stay. Unfortunately, there are no clear external signs and changes associated with a high pressure in the abdomen which could be interpreted as a warning signal. However, the healing process of the affected patient can be delayed severely or even fail in the worst case.
For this reason, we are looking for appropriate diagnostic methods that will help to identify an increased intra-abdominal pressure (IAP) in children early and reliably, without the need for unpleasant additional examinations.
Different direct and indirect methods for the measurement of intra-abdominal pressures are available. In the present study we want to measure the IAP via feeding tubes and / or bladder catheters and / or abdominal drainage or dialysis catheters, respectively (depending on which of these catheters or probes are required anyway due to the underlying illness of the critical ill children).
In addition, we will monitor the blood circulation of the whole body and several abdominal organs using different measure methods (including ultrasound-dilution technique to quantify the circulating blood volume per minute as a measure of total circulatory function (macrocirculation) and including color duplex sonographic examinations of all abdominal organs to estimate the microcirculation). Additionally, the oxygen supply to the organs can be monitored using (near) infrared spectroscopy through the skin (non-invasive). Therefore, additional probes are applied to the skin over the respective organ through which the measurement can be performed completely painless. In blood, urine and other body fluids, we will look for specific proteins and nucleic acids, which can be released at the earliest in cases of pressure-induced tissue or organ damage and may serve as early biomarkers. This will help to define the height of an individual harmful intra-abdominal hypertension and to accelerate the onset of an appropriate therapy.

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Brief Summary in Scientific Language

Almost every critically ill child is in danger to develop intra-abdominal hypertension (IAH) or abdominal compartment Syndrome (ACS) due to diseases concerning the abdominal cavity and abdominal organs or systemic inflammatory states. As a consequence, ACS is able to cause multiple organ failure and death.
Three groups of factors complicate an adequate diagnosis and timely initiation of treatment in the presence or development of IAH and ACS. These include (1) limitations of the quantification of intra-abdominal pressures (IAP) including the rare acceptance for regular IAP measurements, (2) the lack of non-invasive examination methods for the monitoring of microcirculation and organ perfusion particularly under the suppressive influence of increased IAP, and (3) the hitherto fruitless search for laboratory early warning parameters (biomarkers), by which the transition to an IAP-induced organ dysfunction might be detected before the onset of an ischemia-triggered systemic inflammation and potentially irreversible vicious circle with multi-organ failure and death.
The aim of this study is therefore (1) the validation of a continuous IAP measurement method via the stomach in children which might be superior to the intermittent bladder pressure measurements which is currently considered the standard method of IAP monitoring in pediatric patients. To this end, IAP will be measured using both direct and indirect methods (through the stomach and bladder) and the measurement results will be correlated against each other.
(2) the establishment of the basis for the analysis duplexsonographischer findings dynamic Gewebeperfusionsmessung (DTPM; PixelFlux ®) and somatic near-infrared spectroscopy (NIRS) as a tool for non-invasive monitoring of the microcirculation parenchymatous organs under IAH / ACS and (3) the identification of laboratory chemical biomarkers to more timely detection of IAD-induced ischemia and organ damage (promising candidates: intestinal and hepatic fatty acid binding protein (IFABP, hFABP), citrulline and zonulin, various microRNA). The data obtained should contribute to early and reliable diagnosis critical limitations of the micro and macro circulation under IAH / ACS and thereby reduce the high morbidity and mortality.

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Organizational Data

  •   DRKS00006556
  •   2014/09/12
  •   [---]*
  •   yes
  •   Approved
  •   6677, Ethikkommission der Medizinischen Hochschule Hannover
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Secondary IDs

  • [---]*
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Health Condition or Problem studied

  •   R19.0 -  Intra-abdominal and pelvic swelling, mass and lump
  •   R10.0 -  Acute abdomen
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Interventions/Observational Groups

  •   All children and adolescents who are admitted to the interdisciplinary intensive care unit and whose characteristics are consistent with the inclusion criteria. The intra-abdominal pressure is measured directly and indirectly in each subject (via the stomach and via the urinary bladder). The resulting results are correlated with each other and the quality, sensitivity and reliability of the indirect measurement methods will be examined by comparison with direct pressure measures. In addition, micro- and macro-circulation will be monitored in all subjects using global hemodynamic measurement methods, PixelFlux and NIRS. Changes in perfusion and microcirculation are brought into relation with the respective IAP-levels and any mutual influences will be analyzed. Laboratory chemical standard parameters (such as blood count, transaminases, retention parameters, pancreatic enzymes, inflammatory markers) and blood gas analyses as well as the extent of medical assistance are recorded to detect the degree of organ dysfunction and systemic inflammation. Depending on all the above mentioned parameters different proteins and microRNA's are to be identified as potential biomarkers.
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Correlation of directly measured intra-abdominal pressures with indirect measuring methods (via the stomach and bladder) and assessment in terms of accuracy (goodness of fit), sensitivity and practicality. Using gastric tubes the IAP can be determined continuously; via the bladder or using direct accesses, however, the IAP can be examined only intermittently. The proposal provides for hourly documentation of continuous readings and a two-hourly collection and documentation of discontinuous IAP-values.

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Secondary Outcome

Investigation of the influence of different intra-abdominal pressures on global hemodynamics and microcirculation in critically ill children. In addition to established intensive care Parameters at least three times daily cardiac output and other volumetric parameters will be determined using the ultrasound dilution technique (macrocirculation). Duplex ultrasound studies of the microcirculation in parenchymal organs are also done three times a day, which later can be evaluated and quantied using the PixelFlux software. Using somatic optodes, tissue oxygen saturation in parenchymal organs will be continuously monitored with the help of near-infrared spectroscopy (NIRS). The results of NIRS determination will be compared with central venous saturations at least 4x daily . In addition to established laboratory chemical organ parameters, the Proteins zonulin and citrulline, as well as different fatty acid binding proteins and micro-RNAs are regularly determined to thereby establish new biomarkers for the early detection of IAP-induced organ and tissue damage.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2015/05/04
  •   150
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   38   Weeks of pregnancy
  •   18   Years
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Additional Inclusion Criteria

All term infants and pediatric patients between 0 and 18 years of life who are taken to the interdisciplinary pediatric intensive care unit of the Medical University of Hannover and who need anyway - due to their illness or treatment - an abdominal drainage (wound or ascites drainage, peritoneal dialysis catheter etc.) and a gastric tube and / or a urinary catheter might be included in this study. For this purpose, patients and parents are informed in detail about the nature, meaning and objectives of the study and must have expressly agreed to their participation and transmitted a written consent form before the start of measurements. Against the background of nasopharyngeal and esophagogastric proportions formerly preterms can not be included in the study before reaching the expected delivery date in cases of then newly emerging risk factors and new-onset intra-abdominal hypertension.
Preferably, IAP should be measured in children and adolescents at risk for the development of intra-abdominal hypertension (IAH). Related risk factors include all disease entities associated with a pathology and especially inflammation of the abdominal and retroperitoneal spaces or therein located organs and tissues (eg, peritonitis, perforation, pancreatitis, ileus, volvulus, necrotizing / infectious enterocolitis, hemorrhage, tumor / space-occupying processes). Abdominal wall closures (in cases of congenital abdominal wall or diaphragmatic hernia) and "large-for-size" organ transplants are considered "prototypes" of IAH-inducing diseases, since the intra-abdominal filling volume required for a tension-free abdominal closure is insufficient (especially in neonatal patients). Intra-parenchymal and cavitary fluid collections that are observed particularly in the context of capillary leak due to sepsis and systemic inflammation are the most common cause group for IAH and ACS in childhood [Beck 2001]. In addition, hypothermia, positive balance, (mass) transfusions, mechanical ventilation, hypotension and acidosis could be identified as general risk factors for the development of IAH and ACS [Holodinsky 2013, Malbrain 2013].

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Exclusion Criteria

Against the background of nasopharyngeal and esophagogastric size ratios preterm infants (</ = 37 weeks) are excluded from participation in the study to prevent pressure ulcers in the above mentioned areas.
Also excluded are all pediatric patients who have a disease entity of the nasopharynx and / or the upper gastrointestinal tract. These include in particular those children who need surgery or differentiated interventional as well as non-surgical therapies such as dilatation or radiation due to injury, disease or deformity in these areas or have already been operated or treated, respectively. In children and adolescents with a known, suspected or contemporaneous disturbance of the gastric muscle tone as well as following esophageal or gastric surgery (especially anastomosis in esophageal atresia, stomach pull-up, fundoplication or placement of percutaneous endoscopic gastrostomy) no reliable intra-gastric pressure measurement can be expected.
Children and young people with a known or suspected neurogenic bladder dysfunction can be included in the study; however, due to the imperfection of measured intra-vesical pressures bladder pressure measurements must be omitted. All other parameters can be determined, correlated and statistically analyzed.

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Addresses

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    • Medizinische Hochschule Hannover
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
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    • Medizinische Hochschule HannoverZentrum für Kinder- und JugendmedizinKlinik für pädiatrische Kardiologie und Intensivmedizin
    • Mr.  Dr. med.   Torsten   Kaussen 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
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    • Medizinische Hochschule HannoverZentrum für Kinder- und JugendmedizinKlinik für pädiatrische Kardiologie und Intensivmedizin
    • Mr.  Dr. med.   Torsten  Kaussen 
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
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Sources of Monetary or Material Support

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    • Medizinische Hochschule Hannover
    • Carl-Neuberg-Str. 1
    • 30625  Hannover
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.