Background
Methods and design
Study design and outcomes
SDI-PMX-NA001 (EUPHRATES) site IRB list | |||
---|---|---|---|
Site#
|
IRB Chair
|
IRB address
|
Approval date
|
Site #01
| Louis Zeiger, MD | Cooper Health System | 18 Mar 2010 |
Institutional Review Board | |||
Three Cooper Plaza Suite 504 Camden, NJ 08103 | |||
Site #02
| Theodore D Schultz | Western Institutional Review Board | 12 Jul 2010 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #04
(site closed)
| James Linakis | Lifespan Office Research Administration Committee on the Protection of Human Subjects | 17 Sep 2010 |
Rhode Island Hospital Institutional Review Board | |||
593 Eddy St – Aldrich, 5 Providence, Rhode Island 02903 | |||
Site #05
| William Tremaine | Institutional Review Board | 04 Mar 2011 |
Office for Human Research Protection | |||
201 Building, Room 4–60 | |||
200 First Street S.W. | |||
Rochester, Minnesota 55905 | |||
Site #06
| Anne Dougherty, MD | The Committee for the Protection of Human Subjects | 21 Dec 2010 |
6410 Fannin St., Suite 1100 | |||
Houston, TX 77030 | |||
Site #07
| Donald York, PhD | Institutional Review Board | 16 Aug 2010 |
621 S. New Ballas, Suite 6002 | |||
St. Louis, Mo. 63141 | |||
Site #08
| Theodore D Schultz | Western Institutional Review Board | 29 Nov 2010 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #09
| Roger S Wilson, MD | Institutional Review Board/Privacy Board (IRB/PB) | 14 Dec 2010 |
Memorial Sloan Kettering Cancer Center | |||
1275 York Avenue | |||
New York, NY 10065 | |||
Site #10
| Ernest Prentice, PhD | Office of Regulatory Affairs | 13 Dec 2010 |
Institutional Review Board | |||
987830 Nebraska Medical Center | |||
Omaha, NE 68198-7830 | |||
Site #11
| Peter Lichtenthal, MD | Human Subjects Protection Program | 22 Nov 2010 |
1618 E. Helen Street | |||
The University of Arizona | |||
PO Box 245137 | |||
Tucson, AZ 85724 | |||
Site #12
| Glenn Markenson,MD and Rick Granowitz, MD | Baystate Medical Center | 15 Dec 2010 |
Institutional Review Board | |||
759 Chestnut Street | |||
Springfield, MA 01199 | |||
Site #13
| Theodore D Schultz | Western Institutional Review Board | 24 Nov 2010 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #16
| Theodore D Schultz | Western Institutional Review Board | 04 April 2011 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #17
(site closed)
| Theodore D Schultz | Western Institutional Review Board | 11 Apr 2011 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #19
| Craig Scoville, MD, PhD | Eastern Idaho Regional Medical Center IRB | 14 Mar 2011 |
3100 Channing Way | |||
Idaho Falls, ID 83404 | |||
Site #20a and 20b
| Mike Caligiuri | University of California San Diego | 27 Oct 2011 |
9500 Gilman Drive | |||
La Jolla, California 92093 | |||
Site #21
| Jennifer Weinman, BA, MA | Washington University in St. Louis | 21Feb 2012 |
Human Research Protection Office | |||
660 South Euclid Avenue | |||
Campus Box 8089 | |||
St. Louis, MO 63110 | |||
Site #22
| J Bruce Smith, MD, CIP | Thomas Jefferson University Hospital | 20 Oct 2011 |
111 S. 11th Street | |||
Philadelphia, PA 19107 | |||
Site #23a
| Theodore D Schultz | Western Institutional Review Board | 29 Sep 2011 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #23b
| Manoo Bhakta, MD | College of Medicine, Chattanooga | 5 Jul 2012 |
Scientific Review Board | |||
960 East Third Street | |||
Suite 102 | |||
Chattanooga, TN 37403 | |||
Site #25
(site closed)
| John T Promes, MD | Orlando Health | 20 Jan 2012 |
1414 Kuhl Avenue | |||
Orlando, FL 32806 | |||
Site #26
| SKM Kimber, MD, FRCPC | Health Research Ethics Board | 9 Jan 2012 |
308 Campus Towers | |||
University of Alberta | |||
Edmonton, Alberta, Canada T6G 1 KB | |||
Site #27
(site closed)
| Pamela J Oatis, MD | Research Oversight and Education | 29 Feb 2012 |
Mercy St. Vincent Medical Center | |||
2213 Cherry Street | |||
Toledo, OH 43608 | |||
Site #28
(site closed)
| Lois Colliler | Sharp Corondado | 18 Apr 2012 |
Sharp Memorial Hospital | |||
5555 Gossmont Center | |||
La Mesa, CA 91942 | |||
Site #29a
| Russell Bjork, MD | Memorial Health System | 27 Mar 2012 |
1400 East Boulder | |||
Colorado Springs, CO 80909 | |||
Site #29b
| Russell Bjork, MD | Memorial Health System | 26 Oct 2012 |
1400 East Boulder | |||
Colorado Springs, CO 80909 | |||
Site #30
| Philip C Hébert, MD PhD FCFPC | Research Ethics Office, Room C819 | 11 Sep 2012 |
2075 Bayview Avenue | |||
Toronto, ON Canada M4N 3 M5 | |||
Site #31
| JD Miller, MD | System Center-Hazard | 11 Apr 2012 |
100 Airport Gardens Road | |||
Hazard, KY 41701 | |||
Site #32
| Steven Kushner, MD | Helen F. Graham Cancer Center & Research Institute | 01 Jul 2013 |
West Pavilion - Suite 2350 | |||
4701 Ogletown-Stanton Road | |||
Newark, Delaware 19713 | |||
Site #33
| John Hafner Jr, MD | Institutional Review Board | 27 Jun 2012 |
One Illini Drive | |||
Box 1649 | |||
Peoria, IL 61656-1649 | |||
Sites #34a and #34b
| Vivek Singh, MD | Institutional Review Board Office | 09 Aug 2012 |
Mail Code 7830 | |||
7703 Floyd Curl Dr. | |||
San Antonio, TX 78229-3900 | |||
Sites #35a and #35b
| Raphael Saginur, MD | Ottawa Hospital Research Ethics Board | 30 Aug 2012 |
725 Parkdale Ave. | |||
Civic Box 411 | |||
LOEB Building | |||
Ottawa, ON K1Y 4E9 | |||
Site #36
| Allen Korenbilt, MD, CIP | Rush University Medical Center | 31 Oct 2012 |
1653 West Congress Parkway | |||
Chicago, IL 60612-3833 | |||
Site #37
| Theodore D Schultz | Western Institutional Review Board | 17 Sep 2012 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #38
| Theodore D Schultz | Western Institutional Review Board | 24 Jan 2013 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #39
| Leonardo Tamariz, MD, MPH | Human Studies Subcommittee | 19 Sep 2012 |
Miami VA Healthcare System | |||
1201 Northwest 16th St. | |||
Miami, FL 33125-1693 | |||
Site #40
| Theodore D Schultz | Western Institutional Review Board | 17 Jan 2013 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #42
| Jeffrey Silverstein, MD, CIP; | Icahn School of Medicine at Mount Sinai | 01 Feb 2013 |
Glenn Martin, MD, CIP; | One Gustave L. Levy Place | ||
Ilene Wilets, PhD, CIP | Box 1081 | ||
New York, NY 10029-6574 | |||
Site #43
| John Montogomery, Chair | Lakeridge Health | 04 Apr 2013 |
1 Hospital Ct. | |||
Oshawa, ON, Canada L1G 2B9 | |||
Site #44
| SKM Kimber, MD, FRCPC | 308 Campus Tower | 27 Feb 2013 |
University of Alberta | |||
Edmonton, AB T6G 1 K8 | |||
Site #45
| Franck Molin, MD | IUCPQ | 15 Apr 2013 |
2725, Chemin Sainte-Foy | |||
Quebec, QC G1V 4G5 | |||
Site #46
| Alan Lichtin | Cleveland Clinic Foundation | 05 Mar 2013 |
9500 Euclid Ave. | |||
Cleveland, OH 44195 | |||
Site #48
| Timothy Roehrs, PhD | Henry Ford Health System Research Administration | 01 Apr2013 |
2799 West Grand Blvd | |||
CFP-bsmt, room 46 | |||
Detroit, MI 48202 | |||
Site #49
| Stacey A. Page, PhD, Chair, CHREB | Conjoint Health Research Ethics Board (CHREB) | 10 Sep 2013 |
Research Services Office | |||
3rd Floor Mackimmie Library Tower (MLT 300) | |||
2500 University Dr., NW | |||
Calgary, AB, Canada T2N 1 N4 | |||
Site #51
| Ronald Heslegrave, PhD | Mount Sinai Hospital | 03 Jul 2013 |
Research Ethics Board | |||
600 University Ave. | |||
Room 19–311 | |||
Toronto, ON, Canada M5G 1X5 | |||
Site #52a and #52b
| Karen McRae, MD, Co-Chair/Multidisciplinary UHN REB | University Health Network (UHN) | 15 Apr 2013 |
Research Ethics Board (REB) | |||
10th Floor, Room 1056 | |||
700 University Ave. | |||
Toronto, ON, Canada M5G 1Z5 | |||
Site #53
| R Bert Wilkins | Western Institutional Review Board | 22 Jul 2013 |
3535 Seventh Ave. SW | |||
Olympia, WA 98502 | |||
Site #54
| L Wiley Nifong, MD | UMCIRB | 12 Feb 2014 |
East Carolina University | |||
Brody School of Medicine, Brody 4 N-70 | |||
Greenville, NC 27834 | |||
Site #55
| Rhodes L Rigsby, MD | Institutional Review Board | 05 Sep 2013 |
Research Protection Programs | |||
24887 Taylor St. | |||
Suite 202 | |||
Loma Linda, CA 92350 | |||
Site #56
| David Spiegel, MD | Stanford University Research | 12 Jun 2012 |
Compliance Office | |||
1501 South California Ave. | |||
MC: 5579 | |||
Palo Alto, CA 94304 | |||
Site #57
| Ike Eriator, MD | University of Mississippi Medical Center | 12 Feb 2013 |
Institutional Review Board | |||
2500 North State St. | |||
Jackson, MS 39216-4505 | |||
Site #58
| Michael Geisser, PhD, Co-Chair | University of Michigan, IRBMED | 7 Mar 2014 |
2800 Plymouth Road | |||
Building 520, Room 3214 | |||
Ann Arbor, MI 48109-2800 |
Inclusion criteria | Exclusion criteria |
---|---|
Subjects who meet the following criteria (and have a signed informed consent) will be allowed into the study: | 1. Inability to obtain an informed consent from the subject, family member or an authorized surrogate |
1. Age ≥18 years of age | 2. Lack of commitment for full medical support |
2. Hypotension requiring vasopressor support: Requirement for at least one of the vasopressors listed below, at the dose shown below, for at least 2 continuous hours and no more than 30 hours | 3. Inability to achieve or maintain a minimum mean arterial pressure of ≥65 mmHg despite vasopressor therapy and fluid resuscitation |
a. Norepinephrine >0.05 μg/kg/minute | 4. Subject has end-stage renal disease and requires chronic dialysis |
b. Dopamine >10 μg/kg/minute | 5. There is clinical support for non-septic shock such as |
c. Phenylephrine >0.4 μg/kg/minute | a. Acute pulmonary embolus |
d. Epinephrine >0.05 μg/kg/minute | b. Transfusion reaction |
e. Vasopressin >0.03 units/minute | c. Severe congestive heart failure (for example, New York Heart Association Class IV, ejection fraction <35%) |
f. Vasopressin (any dose) in combination with another vasopressor listed above | 6. Subject has had chest compressions as part of cardiopulmonary resuscitation this hospitalization without immediate return to communicative state |
3. The subject must have received intravenous fluid resuscitation of a minimum 30 mL/kg administered within 24 hours of eligibility | |
4. Documented or suspected infection defined as definitive or empiric intravenous antibiotic administration | 7. Subject has had an acute myocardial infarction within the past 4 weeks |
5. Endotoxin activity assay ≥0.60 | 8. Subject has uncontrolled hemorrhage (acute blood loss requiring >3 Units of Packed red blood cellsin the past 24 hours) |
6. Evidence of at least one of the following criteria for new onset organ dysfunction that is considered to be due to the acute illness | 9. Major trauma within 36 hours of screening |
a. Requirement for positive pressure ventilation via an endotracheal tube or tracheostomy tube | 10. Subject has severe granulocytopenia (leukocyte count <500 cells/mm3) or severe thrombocytopenia (platelet count <30,000 cells/mm3) |
b. Thrombocytopenia defined as acute onset of platelet count <150,000 μ/L or a reduction of 50% from prior known levels | 11. HIV infection in association with a last known or suspected CD4 count of <50/mm3
|
c. Acute oliguria defined as urine output <0.5 ml/kg/hour for at least 6 hours despite adequate fluid resuscitation | 12. Subject’s baseline state is non-communicative |
13. Subject has sustained extensive third-degree burns within the past 7 days | |
14. Body weight <35 kg | |
15. Known hypersensitivity to polymyxin B | |
16. Subject has known sensitivity or allergy to heparin or has a history of heparin associated thrombocytopenia | |
17. Subject is currently enrolled in an investigational drug or device trial | |
18. Subject has been previously enrolled in the current trial | |
19. Any other condition, that in the opinion of the investigator, would preclude the subject from being a suitable candidate for enrolment, such as end stage chronic illness with no reasonable expectation of survival to hospital discharge | |
20. Multiple Organ Dysfunction Score ≤9 ** - added post-second interim analysis
|
Vasopressor | Dose Range | Dose Range | Dose Range | Dose Range |
---|---|---|---|---|
1 point | 2 Points | 3 Points | 4 Points | |
Dopamine | 0 dose ≤ 5 | 5 < dose ≤ 10 | 10 < dose ≤ 15 | > 15 |
(mcg/kg/min) | ||||
Epinephrine | - | 0 < dose < 0.05 | 0.05 < dose < 0.1 | > 0.1 |
(mcg/kg/min) | ||||
Norepinephrine | - | 0 < dose < 0.05 | 0.05 < dose < 0.1 | > 0.1 |
(mcg/kg/min) | ||||
Phenylephrine | - | 0 < dose < 0.4 | 0.4 < dose < 0.8 | > 0.8 |
(mcg/kg/min) | ||||
Vasopressin | - | - | - | Any dose |
(units/min) |
1. | To compare mortality between the two groups at 90 days, 6 months and 12 months post-start of treatment |
---|---|
2. | To compare the change in endotoxin levels between the PMX cartridge-treated group and the control group at 12 hours after completion of a second PMX cartridge, with a treatment target of ≥15% reduction of EAA levels with PMX cartridge treatment |
3. | To compare the changes in vasopressor doses for the two groups from day 0 to day 3 |
4. | To compare the number of days of need for vasopressors in each group from day 0 to day 28 (days alive and off vasopressors) |
5. | To compare changes in mean arterial blood pressure for the two groups from day 0 to day 3 |
6. | Comparison of the changes in renal function from day 0 to day 3: |
i. | Fluid balance including urine output |
ii. | Serum creatinine |
7. | To compare the effects of two uses of the PMX cartridge on progression of, and recovery from, organ dysfunction using the multiple organ dysfunction score from day 0 to day 3 |
8. | To compare the number of days of need for renal replacement therapy in each group from day 0 to day 28 (days alive and off renal replacement therapy) |
9. | To compare the number of days of need for mechanical ventilation in each group from day 0 to day 28 (days alive and off mechanical ventilation) |
10. | To compare the mean number of days spent in hospital by subjects in each group for survivors to day 28 |
11. | To compare survival time from baseline to death within 28 days and compare the risk of death between the two study arms |
12. | To compare survival time from baseline to death within 90 days and compare the risk of death between the two study arms |