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| ID | Type | Description | Link |
|---|---|---|---|
| EudraCT-No: 2007-001831-73 |
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| Name | Class |
|---|---|
| Fresenius Kabi | INDUSTRY |
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The purpose of this study is to determine whether providing high dose glutamine and antioxidants to critically ill patients will be associated with improved survival.
Background:
Critically ill patients experience a degree of hyperinflammation, cellular immune dysfunction, and oxidative stress. Supplementation with key nutrients, like glutamine and antioxidants, is most likely to have a favourable effect on these physiological parameters leading to an improvement in clinical outcomes. The results of two separate meta-analyses suggested that glutamine and antioxidants may be associated with improved survival. We have recently completed a dosing study to determine the maximal tolerable dose (MTD) of glutamine dipeptides and antioxidants in critically ill patients with evidence of hypoperfusion. The purpose of this protocol is to evaluate the effect of high dose glutamine and antioxidant supplementation on mortality in a large scale randomized trial.
Study Intervention:
Patients will be randomized to receive glutamine supplementation or antioxidant supplementation (or respective placebo).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glutamine | Experimental | Glutamine supplementation |
|
| Antioxidants | Experimental | Antioxidant supplementation |
|
| Glutamine + Antioxidants | Experimental | Glutamine and antioxidant supplementation |
|
| Placebo | Placebo Comparator | Non-isonitrogenic, iso-caloric placebo solution |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glutamine | Other | 0.35 gm/kg/day parenterally and 30 gms/day enterally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 28-day Mortality | 28-day mortality/status: at 28 days after randomization; | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| ICU Length of Stay | Measure of the duration of participant stay in the ICU | Day 28 |
| ICU Acquired Infection | We have made some modifications the definitions developed by the International Sepsis Forum Consensus Conference (CCM 2005;33:1538-1548) to operationalize the adjudication of infections in this trial. We grade the certainty of the diagnosis of infection using definitions for 'Definite', 'Probable', and 'Possible' for each category of infection. The categories of infection are: Deep surgical wound infection, Incisional (or superficial) surgical wound infection, Skin and soft-tissue infection (non-surgical) (SSTS), Catheter-related blood stream infections (CRI), Primary blood stream infections (BSI), Lower urinary tract infection, Upper urinary tract infection, Intra abdominal infection, Sinusitis, Lower respiratory tract infection (excluding pneumonia), ICU Acquired Pneumonia and Other. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daren Heyland, MD | Clinical Evaluation Research Unit, Kingston General Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Univ. of Colorado at Denver and Health Sciences Center | Aurora | Colorado | 80045 | United States | ||
| University of Louisville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12971736 | Background | Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P; Canadian Critical Care Clinical Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003 Sep-Oct;27(5):355-73. doi: 10.1177/0148607103027005355. | |
| 15605227 |
| Label | URL |
|---|---|
| Click here for more information about this study: A Randomized Trial of Glutamine and Antioxidant Supplementation in Critically Ill Patients | View source |
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Written informed consent was obtained from patients or their legal representatives before enrollment.
This trial was conducted between April 2005 and December 2011 in 40 ICUs in participating countries after local jurisdictional and institutional Research Ethics Board approval.
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| ID | Title | Description |
|---|---|---|
| FG000 | Glutamine | Glutamine supplementation 0.35 g/kg/day of glutamine intravenously based on ideal body weight, provided as 0.50 g/kg/day of the dipeptide alanyl-glutamine and 30 g/day enterally, provided as alanyl-glutamine and glycine-glutamine dipeptides. |
| FG001 | Antioxidants |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Antioxidants |
| Other |
500 micrograms of selenium/day parenterally and selenium 300 microgram, zinc 20 mg, beta carotene 10 mg, vitamine E 500 mg and vitamin C 1500 mg per day enterally |
|
| Glutamine + Antioxidants | Other | 0.35 g/kg/day glutamine parenterally and 30 g/day of glutamine enterally. 500 mcg selenium parenterally plus the following administered enterally: selenium 300 mcg, zing 20 mg, beta-carotene 10 mg, vitamin E 500 mg and vitamin C 1500mg |
|
|
| Placebo | Other | Normal saline intravenously and EN placebo formula (from Fresenius Kabi, Germany) |
|
| Day 28 |
| Hospital Length of Stay | Measure of the duration of the participant's hospital stay | 6 months (from ICU admission) |
| Louisville |
| Kentucky |
| 40202 |
| United States |
| Miami Valley Hospital | Dayton | Ohio | 45409 | United States |
| University of Texas | Houston | Texas | 6431 | United States |
| Fletcher Allan Centre | Burlington | Vermont | 05401 | United States |
| UZ Brussels | Brussels | Belgium |
| University Hospital | Liège | B-4000 | Belgium |
| Royal Alexandra Hospital | Edmonton | Alberta | T5H 3V9 | Canada |
| Grey Nun's Hospital, Edmonton | Edmonton | Alberta | T6L 5X8 | Canada |
| Vancouver Hospital | Vancouver | British Columbia | V5Z 1C6 | Canada |
| St Paul's Hospital | Vancouver | British Columbia | V6Z 1Y6 | Canada |
| Royal Jubilee Hospital | Victoria | British Columbia | V8R 1J8 | Canada |
| Victoria General Hospital | Victoria | British Columbia | V8Z 6R5 | Canada |
| St. Boniface General Hospital | Winnipeg | Manitoba | R2H 2A6 | Canada |
| Health Science Centre | Winnipeg | Manitoba | R3A 1R9 | Canada |
| Capital Health Queen Elizabeth II HSC | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| St Joseph's Healthcare | Hamilton | Ontario | L8N 4A6 | Canada |
| Kingston General Hospital | Kingston | Ontario | K7L 2V7 | Canada |
| London HSC Victoria Campus, ON | London | Ontario | N6A 5W9 | Canada |
| Ottawa Hospital | Ottawa | Ontario | K1H 8H6 | Canada |
| Ottawa Hospital Civic Hospital | Ottawa | Ontario | K1Y 4E9 | Canada |
| Sunnybrook & Women's College, Toronto | Toronto | Ontario | M4N 3M5 | Canada |
| Mt Sinai Hospital | Toronto | Ontario | M5G 1X5 | Canada |
| Hopital Maisonneuve-Rosemount | Montreal | Quebec | H1T 2M4 | Canada |
| Royal Victoria Hospital | Montreal | Quebec | H3A 1A1 | Canada |
| Montreal General | Montreal | Quebec | H3G 1A4 | Canada |
| Hopital de Sacre-Coeur | Montreal | Quebec | H4J 1C5 | Canada |
| Enfant-Jesus | Québec | G1J 1Z4 | Canada |
| Universitatsklinikum der Ernst-Moritz-Arndt-Universitat | Greifswald | Germany |
| Asklepios Kliniken Hamburg Altona | Hamburg | Germany |
| University Medical Center Schleswig-Holstein | Kiel | 24105 | Germany |
| Universitatsklinikum Schleswig-Holstein Campus Luebeck | Lübeck | Germany |
| CHUV | Lausanne | Ch-1011 | Switzerland |
| University of Zurich | Zurich | Switzerland |
| Heyland DK, Dhaliwal R, Suchner U, Berger MM. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med. 2005 Mar;31(3):327-37. doi: 10.1007/s00134-004-2522-z. Epub 2004 Dec 17. |
| 12352035 | Background | Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med. 2002 Sep;30(9):2022-9. doi: 10.1097/00003246-200209000-00011. |
| 23594003 | Result | Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722. |
| 24803474 | Derived | Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M, Muscedere J, Jones G, Day AG; Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enteral Nutr. 2015 May;39(4):401-9. doi: 10.1177/0148607114529994. Epub 2014 May 5. |
Antioxidant supplementation 500 ug of selenium intravenously, and the following vitamins and minerals enterally-- selenium 300 g, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg. |
| FG002 | Glutamine + Antioxidants | Glutamine and antioxidant supplementation 0.35 g/kg/day of glutamine intravenously based on ideal body weight, provided as 0.50 g/kg/day of the dipeptide alanyl-glutamine and 30 g/day enterally, provided as alanyl-glutamine and glycine-glutamine dipeptides. 500 ug of selenium intravenously , and the following vitamins and minerals enterally-- selenium 300 g, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg. |
| FG003 | Placebo | Non-isonitrogenic, iso-caloric placebo solution |
| COMPLETED |
|
| NOT COMPLETED |
|
Five randomized patients were not evaluable because we could not ascertain their 28-day vital status leaving 1218 patients in the final intention-to-treat analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Glutamine | Glutamine supplementation |
| BG001 | Antioxidants | Antioxidant supplementation |
| BG002 | Glutamine + Antioxidants | Glutamine and antioxidant supplementation |
| BG003 | Placebo | Non-isonitrogenic, iso-caloric placebo solution |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 28-day Mortality | 28-day mortality/status: at 28 days after randomization; | Posted | Number | participants | Day 28 |
|
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | ICU Length of Stay | Measure of the duration of participant stay in the ICU | Posted | Median | Inter-Quartile Range | days | Day 28 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | ICU Acquired Infection | We have made some modifications the definitions developed by the International Sepsis Forum Consensus Conference (CCM 2005;33:1538-1548) to operationalize the adjudication of infections in this trial. We grade the certainty of the diagnosis of infection using definitions for 'Definite', 'Probable', and 'Possible' for each category of infection. The categories of infection are: Deep surgical wound infection, Incisional (or superficial) surgical wound infection, Skin and soft-tissue infection (non-surgical) (SSTS), Catheter-related blood stream infections (CRI), Primary blood stream infections (BSI), Lower urinary tract infection, Upper urinary tract infection, Intra abdominal infection, Sinusitis, Lower respiratory tract infection (excluding pneumonia), ICU Acquired Pneumonia and Other. | Posted | Number | participants | Day 28 |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Hospital Length of Stay | Measure of the duration of the participant's hospital stay | Posted | Median | Inter-Quartile Range | days | 6 months (from ICU admission) |
|
|
April 2005 and December 2011
We collect data related to these hospitalized, critically ill patients' baseline illness in the CRF (e.g. abnormalities in oxygenation or ventilation, hemodynamic measures, etc). We reported changes in patients' baseline condition, events that are inconsistent with the underlying pathophysiology or progression of underlying disease, as SAEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Glutamine | Glutamine supplementation 0.35 g/kg/day of glutamine intravenously based on ideal body weight, provided as 0.50 g/kg/day of the dipeptide alanyl-glutamine and 30 g/day enterally, provided as alanyl-glutamine and glycine-glutamine dipeptides. | 14 | 301 | 0 | 301 | ||
| EG001 | Antioxidants | Antioxidant supplementation 500 ug of selenium intravenously and the following vitamins and minerals enterally-- selenium 300 ug, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg. | 11 | 307 | 0 | 307 | ||
| EG002 | Glutamine + Antioxidants | Glutamine and antioxidant supplementation 0.35 g/kg/day of glutamine intravenously based on ideal body weight, provided as 0.50 g/kg/day of the dipeptide alanyl-glutamine and 30 g/day enterally, provided as alanyl-glutamine and glycine-glutamine dipeptides. 500 ug of selenium intravenously and the following vitamins and minerals enterally-- selenium 300 ug, zinc 20 mg, beta carotene 10 mg, vitamin E 500 mg, and vitamin C 1500 mg. | 11 | 310 | 0 | 310 | ||
| EG003 | Placebo | Non-isonitrogenic, iso-caloric placebo solution | 10 | 300 | 0 | 300 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nervous System Disorders | Nervous system disorders | Systematic Assessment |
| ||
| Respiratory Disorders | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Cardiac Disorders | Cardiac disorders | Systematic Assessment |
| ||
| GI Disease | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hepatobiliary Disorders | Hepatobiliary disorders | Systematic Assessment |
| ||
| Vascular Disorders | Vascular disorders | Systematic Assessment |
| ||
| Eye Disorders | Eye disorders | Systematic Assessment |
| ||
| Procedural Complications | Surgical and medical procedures | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Daren Heyland | Clinical Evaluation Research Unit | 613-549-6666 | 4847 | dkh2@queensu.ca |
| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D018805 | Sepsis |
| D009102 | Multiple Organ Failure |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D005973 | Glutamine |
| D000975 | Antioxidants |
| C054122 | alanylglutamine |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
| D021542 | Amino Acids, Neutral |
| D001685 | Biological Factors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D020011 | Protective Agents |
| D045505 | Physiological Effects of Drugs |
| D020313 | Specialty Uses of Chemicals |
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| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| United States |
|
| Germany |
|
| Belgium |
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| Switzerland |
|
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| OG003 | No Antioxidants | Non-isonitrogenic, iso-caloric placebo solution |
|
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|