Cardiovascular ComplicationNCT01413815
Effect of the Amino Acid L-arginine on Perioperative Cardio-vascular Risk in Non-selected Patients
A study testing L-arginine in people with Cardiovascular Complication, run by Universitätsklinikum Hamburg-Eppendorf at 5 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Cardiovascular Complication
- What is being tested?
- L-arginine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 269 participants
- Where
- 5 sitesGermany
- Study dates
- Oct 2010to Sep 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 10Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Institut für Experimentelle und Klinische Pharmakologie,Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie,Kath. Marienkrankenhaus gGmbH
Hamburg, 20246
Klinik und Poliklinik für Anästhesiologie, Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Klinik für Anästhesie und operative Intensivmedizin,Asklepios Klinik Nord, Standort Heidberg
Hamburg, 22417
Klinik für Anästhesiologie,Städtisches Klinikum Lüneburg
Lüneburg, Lower Saxony, 21339
About this study
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.
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.
Read the 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.
- Conditions
- Cardiovascular Complication
- Being tested
- L-arginine, Placebo
- Keywords
- peri-operative, cardiovascular risk, oral supplementation, amino acid L-arginine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDietary 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).
PlaceboOther
Also called corn starch
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)
| Study group | Role | What they receive |
|---|---|---|
| L-arginine | Active comparator | L-Arginine Receives: Dietary Supplement: L-arginine |
| corn starch | Placebo comparator | Placebo: Corn Starch Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: period of 30 days after surgery
Secondary outcomes (4)
difference in incidence between L-arginine and placebo (subgroup with ADMA)
difference in incidence between L-arginine and placebo for the subgroups with ADMA below and above the median concentration
Measured: period of 30 days after surgery
difference in incidence between beta-blocker or no beta-blocker treatment
the difference in incidence of the combined primary end-point between patients on beta-blocker treatment or not on beta-blocker treatment
Measured: period of 30 days after surgery
difference in incidence between statin treatment or no statine treatment
the difference in incidence of the combined primary end-point between patients on statin treatment or not on statin treatment
Measured: period of 30 days after surgery
difference in incidence between L-arginine and placebo (ASA class)
-the difference in incidence of the combined primary end-point between L-arginine and placebo for each of the ASA classes II to IV
Measured: period of 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2011 (estimated)
- Study startOct 2010
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular ComplicationStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 269 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rainer H. Böger, Professor, Principal investigator, Universitätsklinikum Hamburg-Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01413815
- Sponsor's protocol ID
- UKE-KP 2009/001
- Status last verified
- Jun 2022
- First submitted
- 9 Aug 2011
- Last updated
- 1 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17581491Appel 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.
PubMed 32842812
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01413815
- Acronym / sponsor ID
- UKE-KP 2009/001
- Conditions
- Cardiovascular Complication
- Keywords
- peri-operative, cardiovascular risk, oral supplementation, amino acid L-arginine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 269 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 10 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-arginine | Active comparator | Dietary Supplement: L-arginineL-Arginine |
| corn starch | Placebo comparator | Other: PlaceboPlacebo: Corn Starch |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginine3.3 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). | Dietary supplement | L-arginine |
| PlaceboAlso: corn starch3.3 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 | corn starch |
Primary outcome
difference in incidence of the combined end-point of death of any cause
Time frame: period of 30 days after surgery
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.
4 secondary outcomes
difference in incidence between L-arginine and placebo (subgroup with ADMA)
Time frame: period of 30 days after surgery
difference in incidence between beta-blocker or no beta-blocker treatment
Time frame: period of 30 days after surgery
difference in incidence between statin treatment or no statine treatment
Time frame: period of 30 days after surgery
difference in incidence between L-arginine and placebo (ASA class)
Time frame: period of 30 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
- Background: PubMed 17581491Maas 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.
- Results publication: PubMed 32842812Appel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer H. Böger, Professor principal investigator
Universitätsklinikum Hamburg-Eppendorf
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-arginine in people with Cardiovascular Complication, run by Universitätsklinikum Hamburg-Eppendorf at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
difference in incidence of the combined end-point of death of any cause (time frame: period of 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01413815, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2022.