Effect of the Amino Acid L-arginine on Perioperative Cardio-vascular Risk in Non-selected Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Universitätsklinikum Hamburg-Eppendorf.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01413815
First received: August 9, 2011
Last updated: NA
Last verified: August 2011
History: No changes posted
  Purpose

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.


Condition Intervention
Cardiovascular Complication
Dietary Supplement: L-arginine
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Oral Supplementation With the Amino Acid L-arginine on Peri- Operative Cardio-vascular Risk in Non-selected Patients - Role of Pre-operative Determination of Plasma ADMA Levels for Therapeutic Stratification.

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • difference in incidence of the combined end-point of death of any cause [ Time Frame: period of 30 days after surgery ] [ Designated as safety issue: No ]
    the difference in incidence of the combined end-point of death of any cause, acute myocardial infarction or acute coronary syndrome, decompensated heart failure, cardiac arrest or resuscitation, and cerebral or pulmonary embolism between L-arginine and placebo.


Secondary Outcome Measures:
  • difference in incidence between L-arginine and placebo (subgroup with ADMA) [ Time Frame: period of 30 days after surgery ] [ Designated as safety issue: No ]
    difference in incidence between L-arginine and placebo for the subgroups with ADMA below and above the median concentration

  • difference in incidence between beta-blocker or no beta-blocker treatment [ Time Frame: period of 30 days after surgery ] [ Designated as safety issue: No ]
    the difference in incidence of the combined primary end-point between patients on beta-blocker treatment or not on beta-blocker treatment

  • difference in incidence between statin treatment or no statine treatment [ Time Frame: period of 30 days after surgery ] [ Designated as safety issue: No ]
    the difference in incidence of the combined primary end-point between patients on statin treatment or not on statin treatment

  • difference in incidence between L-arginine and placebo (ASA class) [ Time Frame: period of 30 days after surgery ] [ Designated as safety issue: No ]
    -the difference in incidence of the combined primary end-point between L-arginine and placebo for each of the ASA classes II to IV


Estimated Enrollment: 640
Study Start Date: October 2010
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: L-arginine Dietary Supplement: L-arginine
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).
Placebo Comparator: corn starch Other: Placebo
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 Name: corn starch

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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male and female subjects aged between 30 and 75 years;
  • scheduled major thoracic (non-cardiac), abdominal, or two cavity surgery;
  • ASA risk class II- IV;
  • efficient birth control for women in child-bearing age;
  • signed written informed consent form.

Exclusion Criteria:

  • participation in a clinical study within the last 3 months before inclusion into the present study;
  • high allergic tendency in the medical history at the investigators discretion;
  • patients with known diabetic retinopathy;
  • previous abuse of drugs or alcohol;
  • pregnancy or nursing;
  • any severe consuming disease (malignant or non-malignant) that reduces the patient's life expectancy to a level which makes it uncertain that the patient would survive the 30 day period even without surgery;
  • any somatic or psychic disease that may hamper participation in the study or compliance;
  • active liver disease or hepatic failure (serum AST or ALT >1.5-fold above the upper limit of the normal range);
  • severe renal failure (calculated creatinine clearance < 30 ml/min [Cockcroft-Gault formula]), nephrotic syndrome or dysproteinemia;
  • previous intolerance of L-arginine or L-citrulline.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01413815

Contacts
Contact: Rainer H. Böger, Professor +49 40 7410 59759 boeger@uke.uni-hamburg.de

Locations
Germany
Klinik für Anästhesiologie,Städtisches Klinikum Lüneburg Recruiting
Lüneburg, Niedersachsen, Germany, 21339
Contact: C. Frenkel, Professor    +49 4131 77 22 20      
Principal Investigator: C. Frenkel, Professor         
Sub-Investigator: Michael Letschat         
Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Daniel Appel, MD    +49 40 7410 52415      
Principal Investigator: Daniel Appel, MD         
Sub-Investigator: Alwin E. Goetz, Professor         
Sub-Investigator: Matthias Göpfert, MD         
Klinik für Anästhesie und operative Intensivmedizin,Asklepios Klinik Nord, Standort Heidberg Recruiting
Hamburg, Germany, 22417
Contact: Oliver Detsch, MD    +49 40 1887 3720    o.detsch@asklepios.com   
Principal Investigator: Oliver Detsch, MD         
Sub-Investigator: Mrs. Danel         
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie,Kath. Marienkrankenhaus gGmbH Recruiting
Hamburg, Germany, 20246
Contact: Norbert Rolf, Professor    + 49 40 2546 1102      
Principal Investigator: Norbert Rolf, Professor         
Institut für Experimentelle und Klinische Pharmakologie,Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Rainer H. Böger, Professor    +49 40 7410 59759    boeger@uke.uni-hamburg.de   
Sub-Investigator: Meike Anderssohn, MD         
Principal Investigator: Rainer H. Böger, Professor         
Sub-Investigator: Nicole Lüneburg, MD         
Sub-Investigator: Edzard Schwedhelm, MD         
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Principal Investigator: Rainer H. Böger, Professor Universitätsklinikum Hamburg-Eppendorf
  More Information

Publications:
Responsible Party: Prof. Dr. Rainer H. Böger, Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01413815     History of Changes
Other Study ID Numbers: UKE-KP 2009/001
Study First Received: August 9, 2011
Last Updated: August 9, 2011
Health Authority: Germany: Ethics Commission

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
peri-operative
cardiovascular risk
oral supplementation
amino acid L-arginine

ClinicalTrials.gov processed this record on July 22, 2014