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

NCT01413815 | Completed DMC

• 1 other identifier: UKE-KP 2009/001
• Study Type: interventional
• Target: 269
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Cardiovascular Complication

Keywords

peri-operative; cardiovascular risk; oral supplementation; amino acid L-arginine

Outcome Measures

Primary Outcomes (1)

• difference in incidence of the combined end-point of death of any cause

  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.

  period of 30 days after surgery

Secondary Outcomes (4)

• difference in incidence between L-arginine and placebo (subgroup with ADMA)

  period of 30 days after surgery

• difference in incidence between beta-blocker or no beta-blocker treatment

  period of 30 days after surgery

• difference in incidence between statin treatment or no statine treatment

  period of 30 days after surgery

• difference in incidence between L-arginine and placebo (ASA class)

  period of 30 days after surgery

Study Arms (2)

L-arginine

ACTIVE COMPARATOR

L-Arginine

Dietary Supplement: L-arginine

corn starch

PLACEBO COMPARATOR

Placebo: Corn Starch

Other: Placebo

Interventions

L-arginine DIETARY_SUPPLEMENT

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).

L-arginine

Placebo OTHER

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)

Also known as: corn starch

corn starch

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (5)

Klinik für Anästhesiologie,Städtisches Klinikum Lüneburg

Lüneburg, Lower Saxony, 21339, Germany

Location

Institut für Experimentelle und Klinische Pharmakologie,Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie,Kath. Marienkrankenhaus gGmbH

Hamburg, 20246, Germany

Location

Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinik für Anästhesie und operative Intensivmedizin,Asklepios Klinik Nord, Standort Heidberg

Hamburg, 22417, Germany

Location

Related Publications (2)

• Maas R, Dentz L, Schwedhelm E, Thoms W, Kuss O, Hiltmeyer N, Haddad M, Kloss T, Standl T, Boger RH. Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine predict adverse events in patients undergoing noncardiac surgery. Crit Care Med. 2007 Aug;35(8):1876-81. doi: 10.1097/01.CCM.0000277038.11630.71.

  PMID: 17581491 BACKGROUND

• Appel D, Boger R, Windolph J, Heinze G, Goetz AE, Hannemann J. Asymmetric dimethylarginine predicts perioperative cardiovascular complications in patients undergoing medium-to-high risk non-cardiac surgery. J Int Med Res. 2020 Aug;48(8):300060520940450. doi: 10.1177/0300060520940450.

  PMID: 32842812 RESULT

MeSH Terms

Interventions

Arginine; Starch

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• Rainer H. Böger, Professor

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2011
• First Posted: August 10, 2011
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: July 1, 2022

Record last verified: 2022-06

Locations

DE (5)