Effect of the Amino Acid L-arginine on Perioperative Cardio-vascular Risk in Non-selected Patients
Condition: Cardiovascular Complication
Study type: Interventional

Summary: 
      The aim of the study is to test whether pre-operative oral supplementation with L-arginine
      results in a significant reduction of peri-operative cardiovascular complication rate in
      unselected patients undergoing major abdominal or thoracic (non-cardiac) surgery. The second
      aim of the study is to assess whether pre-operative determination of plasma ADMA levels
      allows to identify patients who are at high risk of experiencing a peri-operative
      complication, and whether this subgroup of patients profits specifically from pre-operative
      L-arginine supplementation.
    

Detailed description: 
      Patients will be recruited for this study from the participating Departments. In a previous
      study (protocol no. UKE-KP 2002/006) we investigated the predictive role of ADMA (asymmetric
      dimethylarginine) for peri-operative complications in unselected patients undergoing major
      surgery. The major result of that study was that patients with pre-operative ADMA plasma
      level within the highest quartile of the distribution had a significantly elevated risk of
      experiencing a serious peri-operative complication within a period of 30 days after the
      surgical intervention. These data have been published [Maas et al. 2007]. As ADMA
      competitively displaces L-arginine from the enzyme, NO synthase, it is expected that the
      adverse cardiovascular effects of high ADMA levels can be antagonized by supplemental
      L-arginine. Therefore, the present study was designed to specifically address the question
      whether dietary supplementation with L-arginine before the surgery, aiming at replenishing
      the body's L-arginine stores, may help to reduce the peri- operative complication rate.
      Another aim is to assess whether this occurs in all patients or specifically in the subgroup
      with elevated baseline ADMA levels.

      Study participants will be recruited from patients who routinely visit the outpatient clinic
      at the participating Departments of Anesthesiology and Intensive Care in advance of their
      planned surgical intervention. Patients usually visit the clinic between five working days in
      advance of the scheduled time of surgery, or they are admitted to in-patient treatment one or
      two days before the surgery. They will be informed about the scope and aim of the study, and
      after having given their informed consent, patients will receive L-arginine dietary
      supplements or corresponding placebo according to randomisation plan for the time until
      surgery. The last dosage of the L-arginine supplements will be taken in the morning of the
      surgery, dissolved in a glass of tap water that patients ware required to drink with
      premedication for anesthesia. Blood samples to measure plasma L-arginine and ADMA levels will
      be taken at the time of inclusion, in the morning before scheduled surgery, and on days 1 and
      3 after the surgery and will together with additional safety parameter not exceed 80ml. No
      administration of study product will occur after surgery.

      After surgery having taken place, patients will be monitored daily for as long as they remain
      being treated as in-patients, and all clinical events, changes in laboratory parameters, and
      apparatively performed clinical tests as scheduled according to clinical routine will be
      documented. No additional clinical treating will be performed on study participants, except
      the blood samples that will be taken as described above. After discharge, patients will be
      followed-up telephonically, for the last time at 30 days after the date of surgery. All
      clinical events occurring in this period will be recorded. In addition, changes in laboratory
      values, ECG recordings, and other apparative diagnostic measures will be checked for possible
      complications, and also be recorded.
    

Intervention name(s): L-arginine; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 3.3 g of L-arginine capsules, oral,b.i.d for a period of three days (a variability ±2 days is accepted to enable scheduling of surgery according to requirements of clinical routine).; 3.3 g of placebo capsules/ b.i.d.; for a period of three days (a variability ±2 days is accepted to enable scheduling of surgery according to requirements of clinical routine)
Other intervention name(s): corn starch
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: peri-operative; cardiovascular risk; oral supplementation; amino acid L-arginine