Trial document




drksid header

  DRKS00000597

Trial Description

start of 1:1-Block title

Title

Does Low-Dose Xenon Reduce Opioid Requirement and Postoperative Pain in Patients Undergoing Major Abdominal Surgery? A Randomized Controlled Trial

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

[---]*

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-d-aspartate receptors (NMDAR). At sub-anesthetic doses the NMDAR antagonist xenon supresses pain-evoked sensitization of pain processing areas in the central nervous system (CNS). While numerous studies describe the effect of NMDAR-antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing.
To analyze the strength of the analgesic effect of low dose xenon using new economical
application methods, we plan to apply xenon in differnet concentrations as an add-on treatment for analgesia in 90 patients undergoing abdominal hysterectomy. Therefore we will measure intra- and postoperative requirement of opioids within a randomized double-blind placebo-controlled study design.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

The N-methyl-d-aspartate receptor (NMDAR) is an excitatory glutamate receptor that is involved in the modulation of prolonged pain states induced by sensitization processes. NMDAR antagonists, such as ketamine and dextromethorphan, have been shown to be useful in the reduction of acute postoperative pain and analgesic consumption. Small doses of NMDAR antagonists led to a reduced
postoperative requirement of opioids and suppressed the development of tolerance to opioids and opioid induced hyperalgesia. Therefore a concomitant application of small doses of NMDAR antagonists within a concept of multimodal analgesia is suggested. The noble gas xenon (Xe) derives its name from the Greek “stranger” because of its rarity,
representing no more than 8.75 x 10-6 % of the atmosphere. For more than 50 years xenon has been used in clinical anesthetic practice and has proven to be a potent inhalation anesthetic with analgesic and organ-protective propertie. The preponderance of evidence is that xenon acts via
noncompetitive inhibition of NMDAR. However, it cannot be ruled out that other targets of
xenon additionally mediate inhibitory effects of the noble gas. Up to now, xenon‟s safety
and efficacy profile appears to be unequalled and only its relatively high costs and limited resources has precluded its widespread clinical use. An optimal pain management is an important part of adequate postoperative care. However, 30–80% of postoperative patients complain about moderate to severe post-surgical pain and inadequate
postoperative pain relief may delay recovery, lead to a prolonged hospital stay, and increase medical costs. In a recently published study we showed an enhanced responsiveness of pain processing areas to repeated painful stimulation using fMRI experiments. This enhancement was suppressed by the NMDAR antagonist xenon at sub-anesthetic doses providing evidence for an involvement of NMDAR in pain evoked synaptic plasticity in the human brain. Moreover, we described the increased pain tolerance induced by xenon applied in a low dosage within a placebo-controlled experimental human study (Adolph et al. 2010; Froeba et al. 2010).
To analyze the strength of the analgesic effect of low dose xenon using new economical application methods within the clinical setting, we will test low dose applied xenon as an add-on treatment for analgesia in patients undergoing abdominal hysterectomy. Therefore we plan the assessment of intra- and postoperative requirement of opioids within a randomized double-blind placebo-controlled study design.

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00000597
  •   2010/10/29
  •   [---]*
  •   yes
  •   Approved
  •   129/11, Ethik-Kommission der Universität Ulm
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   R52 -  Pain, not elsewhere classified
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Placebo (air applied via inhalation); By use of a table of random numbers, patients will be allocated into one of the arms (1-3).
  •   Xenon (10%, applied via inhalation during surgery); By use of a table of random numbers, patients will be allocated into one of the arms (1-3).
  •   Xenon (20%, applied via inhalation during surgery); By use of a table of random numbers, patients will be allocated into one of the arms (1-3).
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Double or multiple blind
  •   [---]*
  •   Placebo, Other
  •   Treatment
  •   Parallel
  •   IIb
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Intra- and postoperative opioid requirement (remifentanil, morphine); patients‟ subjective feeling of pain assessed 0.5, 3, 6, 12, and 24h postoperative using the well known numeric rating scale (NRS).

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

relevant side-effects (e.g. vomiting, increased sedation), economical aspects (e.g. xenon/opioid consumption)

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • [---]*
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Planned
  •   2011/11/01
  •   90
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Female
  •   18   Years
  •   75   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

ASA physical status I and II (NYHA ≤ 1), patients scheduled for elective abdominal hysterectomy at the University Hospital of Ulm

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

Excusion criteria are respiratory tract infections, obstructive sleep apnea, diabetes mellitus, any relevant renal, liver, or heart (including arterial hypertension) disease, a history of neurological or psychiatric disorders or of adverse reactions to anesthetics, gastroesophageal reflux disease, regular alcohol consumption, drug abuse or taking sedatives or long acting analgesic drugs.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Klinik für Anästhesiologie Universitätsklinkum Ulm
    • Mr.  Prof. Dr. med. Dr. med. h.c.  Michael  Georgieff 
    • Steinhövelstr. 9
    • 89073  Ulm
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   0731 500 60 229
    •   0731 500 60 002
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Klinik für Anästhesiologie Universitätsklinkum Ulm
    • Mr.  PD Dr.  Oliver  Adolph 
    • Steinhövelstr. 9
    • 89073  Ulm
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Klinik für Anästhesiologie Universitätsklinkum Ulm
    • Mr.  PD Dr.  Oliver  Adolph 
    • Steinhövelstr. 9
    • 89073  Ulm
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Klinik für Anästhesiologie, Universitätsklinikum Ulm
    • Steinhövelstr. 9
    • 89073  Ulm
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting planned
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.