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| Name | Class |
|---|---|
| Alberta Children's Hospital | OTHER |
| British Columbia Children's Hospital | OTHER |
| London Health Sciences Centre | OTHER |
| St. Justine's Hospital |
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Approximately 20,000 children per year in North America present to the hospital with severe shock. Children who develop this condition have very low blood pressures and as a result may suffer damage to their internal organs and may even die. Some children with this condition may significantly benefit from the use of steroids but steroids in such patients may also have potential side effects. Therefore it is important to study the use of steroids carefully in these children. The STRIPES research program will examine the effectiveness and safety of steroids in children. Before conducting a large, randomized controlled trial (RCT), a pilot study (STRIPES Pilot Study) will be conducted in multiple sites across Canada. The STRIPES Pilot Study will allow testing of the STRIPES study protocol in a smaller group of patients.
This study is a multi-centre pilot RCT to determine the feasibility of doing a full trial on the effect of steroids versus placebo in children with fluid and vasoactive infusion dependent shock. The principal investigator and colleagues recently published two articles on this topic which were selected as the Feature Article and Feature Review in the June edition of Pediatric Critical Care Medicine. Both of these publications strongly support the interest in this area and the accompanying editorial strongly supported the need for a well-designed RCT.
RATIONALE: Approximately 20,000 children per year present to emergency departments, pediatric wards and intensive care units in North America with fluid and vasoactive infusion dependent shock. This severe type of shock results in significant morbidity and carries a 2-10% mortality rate depending on the setting in which it occurs. This form of shock is thought to arise from dysfunction of the hypothalamic-pituitary-adrenal axis through a variety of mechanisms and has been referred to as relative adrenal insufficiency or critical illness related adrenal insufficiency. Many clinicians believe that corticosteroids improve outcomes in such patients and therefore use them when confronted with a critically ill child with fluid and vasoactive infusion dependent shock. However, the effectiveness and safety of steroid replacement therapy in pediatric shock remain to be demonstrated.
OBJECTIVES - PILOT STUDY: Before embarking on a multi-centre definitive trial to address the questions listed above, the STRIPES Pilot Study has 3 specific feasibility objectives: 1) To estimate the rate of patient recruitment and understand barriers to recruitment; 2) To assess adherence to our specific treatment protocol; and 3) To document the frequency of and understand the reasons for open label steroid use.
OBJECTIVES - FULL RCT: Following successful completion of the STRIPES Pilot Study, the next phase will be a large, multi centre RCT to answer the following questions: 1) What is the effect of hydrocortisone versus placebo on the time to discontinuation of vasoactive agents among pediatric patients with fluid and vasoactive infusion dependent shock?; and 2) In patients with fluid and vasoactive infusion dependent shock, what is the effect of hydrocortisone versus placebo on i) pediatric intensive care unit (PICU) mortality; ii) duration of mechanical ventilation; iii) new onset of organ dysfunction; iv) PICU length of stay; and v) incidence of adverse events?
RESEARCH PLAN: The STRIPES Pilot Study is designed as a pragmatic, multi-centre, double blind, RCT of intravenous hydrocortisone versus intravenous placebo in fluid and vasoactive infusion dependent shock. This study aims to enroll 72 patients from 7 pediatric centres across Canada over a one year period. Patients will be recruited from the Emergency Department and the PICU within 6 hours of being stared on a vasoactive agent. Research ethics board approval will be obtained from all participating centres and application for deferred consent will be made at 5 sites. Health Canada approval is not required as hydrocortisone is approved for use in children at the doses and for the indication for which it is being used in this study.
As part of the pragmatic design, the prescriptive component of the protocol will be limited to the administration and weaning of the study drug. The requirement for intubation, mechanical ventilation, sedation and analgesia, use of hemodynamic triggers and endpoints, red cell transfusions, antibiotics and fluid boluses will be left to the discretion of the treating physician. The Surviving Sepsis Guidelines Flowchart will be attached to the study protocol for easy reference by the treating physician but its use will not be mandated; however, the use of vasoactive infusions and other therapies will be recorded. The proposed duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug. Outcome data, including survival status and frequency of adverse events, will be collected daily until discharge from hospital.
Although the primary focus of this pilot study is to determine the feasibility of conducting a clinical outcome based RCT of steroids versus placebo in shock, this pilot also provides an excellent opportunity to perform some exploratory mechanistic studies. These will include 1) comparison of total and free cortisol levels of patients with shock; 2) measurement of stratification biomarkers; and 3) determination of 25 hydroxyvitamin D and 1,25 hydroxyvitamin D levels on admission. Patients with access for blood sampling and for whom consent has been obtained will have blood samples sent for these mechanistic studies.
Patients will be randomized to the hydrocortisone or placebo arm using web-based, centralized permuted block randomization, stratified by centre. All study personnel (the overall study research coordinator, research assistants, site investigators, principal investigator, co-investigators, data management personnel, and statisticians), members of the health care team (treating physicians, bedside nurses, and clinical pharmacists) and patients/families will be blinded to the study group assignment.
SIGNIFICANCE: Results of the STRIPES Pilot Study will provide essential feasibility data for planning and conducting a larger, multi-centre trial that will help to establish the role of steroids in children with fluid and vasoactive infusion dependent shock. There are special challenges to patient recruitment in critically ill pediatric populations, adherence to treatment protocols and to the limitation of open label use of steroids, all of which the STRIPES Pilot study will help to address. Success of the STRIPES Pilot Study will be based on the ability to achieve each of the three feasibility objectives listed above. If the pilot study demonstrates feasibility, no major protocol changes are needed, and no safety concerns are raised by the Data Safety Monitoring Board, then the results of the pilot study will be rolled into the full trial. However, if any of the above criteria are not met, then the protocol will be re-evaluated and the feasibility results of the pilot study published independently.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hydrocortisone | Experimental | Patients randomized to the hydrocortisone arm will receive a 2 mg/kg hydrocortisone IV bolus on enrolment followed by 1 mg/kg of hydrocortisone IV q6h until the patient has not had an escalation in therapy for at least 12 hours. If the patient meets these criteria their hydrocortisone will be weaned to 1 mg/kg every 8 hours which will be continued until they are off all vasoactive infusions for 12 hours. If following the initial hydrocortisone wean, the patient requires fluid boluses and/or an increase in their vasoactive infusion(s), their hydrocortisone will be increased back to 1 mg/kg of hydrocortisone IV q6h until they meet stability criteria again. Duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug. |
|
| Placebo | Placebo Comparator | Patients randomized to the placebo arm will receive a placebo solution consisting of normal saline equivalent in volume to the appropriate dose of hydrocortisone. Hydrocortisone and placebo will be identical in appearance, volume and smell as hydrocortisone is made up in normal saline and dissolves completely with no visible precipitate. The dosing regimen will be identical to the hydrocortisone arm. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrocortisone | Drug | Hydrocortisone will be made up as a 10 mg/ml solution so the volume of added fluid will be very small (2 to 10 mls even for the initial dose of 2 mg/kg). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Patient Accrual Rate Over One Year (% of Target Sample Size Achieved) | The total number of participants recruited over the recruitment period to both arms (this was a feasibility outcome that was analyzed for the full cohort and, as stated a priori in the study protocol was not compared between study arms). Our goal is to recruit 72 patients over one year . However, we will consider patient accrual rate to be adequate if we recruit 60 patients from seven sites within this time period. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 1a. Time to Administration of the First Dose of Study Drug | This objective is a measure of protocol adherence. The goal is to have patients randomized within 6 hours, and study drug administration completed within 8 hours of starting a vasoactive medication. We will consider adherence to our protocol to be adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | 8 hours from starting vasoactive medication |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kusum Menon, MD, MSc | Children's Hospital of Eastern Ontario | Principal Investigator |
| Karen Choong, MB, MSc | McMaster Children's Hospital | Study Chair |
| James D McNally, MD, PhD | Children's Hospital of Eastern Ontario | Study Chair |
| Lauralyn McIntyre, MD, MSc | The Ottawa Hospital | Study Chair |
| Margaret Lawson, MD, MSc | Children's Hospital of Eastern Ontario | Study Chair |
| Hector Wong, MD | Children's Hospital Medical Center, Cincinnati | Study Chair |
| Tim Ramsay, MSc, PhD | Ottawa Hospital Research Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada | ||
| British Columbia Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23628832 | Background | Menon K, McNally JD, Choong K, Ward RE, Lawson ML, Ramsay T, Wong HR. A survey of stated physician practices and beliefs on the use of steroids in pediatric fluid and/or vasoactive infusion-dependent shock. Pediatr Crit Care Med. 2013 Jun;14(5):462-6. doi: 10.1097/PCC.0b013e31828a7287. | |
| 23867428 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Hydrocortisone | Patients randomized to the hydrocortisone arm will receive a 2 mg/kg hydrocortisone IV bolus on enrolment followed by 1 mg/kg of hydrocortisone IV q6h until the patient has not had an escalation in therapy for at least 12 hours. If the patient meets these criteria their hydrocortisone will be weaned to 1 mg/kg every 8 hours which will be continued until they are off all vasoactive infusions for 12 hours. If following the initial hydrocortisone wean, the patient requires fluid boluses and/or an increase in their vasoactive infusion(s), their hydrocortisone will be increased back to 1 mg/kg of hydrocortisone IV q6h until they meet stability criteria again. Duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug. Hydrocortisone: Hydrocortisone will be made up as a 10 mg/ml solution so the volume of added fluid will be very small (2 to 10 mls even for the initial dose of 2 mg/kg). |
| FG001 | Placebo | Patients randomized to the placebo arm will receive a placebo solution consisting of normal saline equivalent in volume to the appropriate dose of hydrocortisone. Hydrocortisone and placebo will be identical in appearance, volume and smell as hydrocortisone is made up in normal saline and dissolves completely with no visible precipitate. The dosing regimen will be identical to the hydrocortisone arm. Placebo: The placebo (normal saline) will be identical in appearance, volume and smell to the active study drug (hydrocortisone). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Hydrocortisone | Patients randomized to the hydrocortisone arm will receive a 2 mg/kg hydrocortisone IV bolus on enrolment followed by 1 mg/kg of hydrocortisone IV q6h until the patient has not had an escalation in therapy for at least 12 hours. If the patient meets these criteria their hydrocortisone will be weaned to 1 mg/kg every 8 hours which will be continued until they are off all vasoactive infusions for 12 hours. If following the initial hydrocortisone wean, the patient requires fluid boluses and/or an increase in their vasoactive infusion(s), their hydrocortisone will be increased back to 1 mg/kg of hydrocortisone IV q6h until they meet stability criteria again. Duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug. Hydrocortisone: Hydrocortisone will be made up as a 10 mg/ml solution so the volume of added fluid will be very small (2 to 10 mls even for the initial dose of 2 mg/kg). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Patient Accrual Rate Over One Year (% of Target Sample Size Achieved) | The total number of participants recruited over the recruitment period to both arms (this was a feasibility outcome that was analyzed for the full cohort and, as stated a priori in the study protocol was not compared between study arms). Our goal is to recruit 72 patients over one year . However, we will consider patient accrual rate to be adequate if we recruit 60 patients from seven sites within this time period. | This feasibility objective, as stated a priori in the protocol, was analyzed for the full study cohort and was not compared between arms. The primary objective was the patient accrual rate over one year (percentage of for the target sample size for the full cohort that was achieved). | Posted | Number | percentage of target sample size | 1 year |
|
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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 | Hydrocortisone | Patients randomized to the hydrocortisone arm will receive a 2 mg/kg hydrocortisone IV bolus on enrolment followed by 1 mg/kg of hydrocortisone IV q6h until the patient has not had an escalation in therapy for at least 12 hours. If the patient meets these criteria their hydrocortisone will be weaned to 1 mg/kg every 8 hours which will be continued until they are off all vasoactive infusions for 12 hours. If following the initial hydrocortisone wean, the patient requires fluid boluses and/or an increase in their vasoactive infusion(s), their hydrocortisone will be increased back to 1 mg/kg of hydrocortisone IV q6h until they meet stability criteria again. Duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug. Hydrocortisone: Hydrocortisone will be made up as a 10 mg/ml solution so the volume of added fluid will be very small (2 to 10 mls even for the initial dose of 2 mg/kg). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal bleeding | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Katie O'Hearn, Research Coordinator | Children's Hospital of Eastern Ontario | 613-737-7600 | 4006 | kohearn@cheo.on.ca |
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| ID | Term |
|---|---|
| D012769 | Shock |
| D000309 | Adrenal Insufficiency |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| C007133 | hydrocortisone hemisuccinate |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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| OTHER |
| IWK Health Centre | OTHER |
| Montreal Children's Hospital of the MUHC | OTHER |
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|
| Placebo | Other | The placebo (normal saline) will be identical in appearance, volume and smell to the active study drug (hydrocortisone). |
|
|
| 1b. Weaning of Study Drug to q8h When Patient is Hemodynamically Stable | This objective is a measure of protocol adherence. The goal is weaning of study drug to q8h within 12 hours of no escalation of therapy. We will consider adherence to our protocol to be adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | 7 days |
| 1c. Discontinuation of Study Drug When Off All Vasoactive Medications | This objective is a measure of protocol adherence. The goal is to discontinue study drug within 12 to 18 hours of vasoactive medications being stopped. We will consider adherence to the protocol adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | 7 days |
| Number of Patients Started on Open Label Steroids by the Treating Physician | We will consider the number of patients started on open label steroids by the treating physician to be acceptable if it occurs in less than 10% of patients. We will also collect information on the clinical parameters of patients when open label steroids are given. | 7 days |
| Time to Discontinuation of Vasoactive Infusions | The time to discontinuation of vasoactive agents will be used to better estimate the sample size for the full study. | Daily during hospital admission (up to 28 days) |
| Number of Participants With Incidence of Adverse Events and Mortality in the Full Cohort | The specific adverse events that will be measured include: severe bleeding, secondary infections and the use of insulin infusions. The incidence of adverse events and mortality rate was measured in aggregate (i.e. the whole cohort) in order to provide a better baseline estimate of these outcomes in our study population. | Daily during hospital admission (up to 28 days) |
| Percentage of Patients for Whom Blood Samples Are Sent, and Successfully Received and Analyzed in Their Respective Labs | A total of 3 ml of blood in a red top tube will be collected within 24 hours of hospital admission. Patients with access for blood sampling and for whom consent has been obtained will have blood samples collected. The samples will be separated at each centre, stored until the end of the recruitment period, and then shipped to the principal investigators's centre as per the specific test requirements. The free cortisol and stratification biomarker samples will be batched and then shipped to Cincinnati for analysis at the end of the study. The number of samples collected, and the number of samples successfully received and analyzed at the principal investigator's site and at the Cincinnati lab will be determined at the end of the recruitment phase. | End of the study recruitment phase (up to 1.5 years) |
| Vancouver |
| British Columbia |
| V6H 3V4 |
| Canada |
| IWK Health Centre | Halifax | Nova Scotia | B3K 6R8 | Canada |
| McMaster Children's Hospital | Hamilton | Ontario | L8N 3Z5 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H8L1 | Canada |
| Montreal Children's Hospital of the MUHC | Montreal | Quebec | H3H 1P3 | Canada |
| Hospital St. Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Menon K, McNally D, Choong K, Sampson M. A systematic review and meta-analysis on the effect of steroids in pediatric shock. Pediatr Crit Care Med. 2013 Jun;14(5):474-80. doi: 10.1097/PCC.0b013e31828a8125. |
| 17332201 | Background | Odetola FO, Gebremariam A, Freed GL. Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis. Pediatrics. 2007 Mar;119(3):487-94. doi: 10.1542/peds.2006-2353. |
| 21897156 | Background | Kissoon N, Carcillo JA, Espinosa V, Argent A, Devictor D, Madden M, Singhi S, van der Voort E, Latour J; Global Sepsis Initiative Vanguard Center Contributors. World Federation of Pediatric Intensive Care and Critical Care Societies: Global Sepsis Initiative. Pediatr Crit Care Med. 2011 Sep;12(5):494-503. doi: 10.1097/PCC.0b013e318207096c. |
| 23361625 | Background | Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30. |
| 20299532 | Background | Menon K, Ward RE, Lawson ML, Gaboury I, Hutchison JS, Hebert PC; Canadian Critical Care Trials Group. A prospective multicenter study of adrenal function in critically ill children. Am J Respir Crit Care Med. 2010 Jul 15;182(2):246-51. doi: 10.1164/rccm.200911-1738OC. Epub 2010 Mar 18. |
| 20721535 | Background | Zimmerman JJ, Barker RM, Jack R. Initial observations regarding free cortisol quantification logistics among critically ill children. Intensive Care Med. 2010 Nov;36(11):1914-22. doi: 10.1007/s00134-010-2007-1. Epub 2010 Aug 19. |
| 19352620 | Background | Poomthavorn P, Lertbunrian R, Preutthipan A, Sriphrapradang A, Khlairit P, Mahachoklertwattana P. Serum free cortisol index, free cortisol, and total cortisol in critically ill children. Intensive Care Med. 2009 Jul;35(7):1281-5. doi: 10.1007/s00134-009-1480-x. Epub 2009 Apr 8. |
| 15084695 | Background | Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004 Apr 15;350(16):1629-38. doi: 10.1056/NEJMoa020266. |
| 8706448 | Background | Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated Pediatric Risk of Mortality score. Crit Care Med. 1996 May;24(5):743-52. doi: 10.1097/00003246-199605000-00004. |
| 21057361 | Background | Zimmerman JJ, Donaldson A, Barker RM, Meert KL, Harrison R, Carcillo JA, Anand KJ, Newth CJ, Berger J, Willson DF, Jack R, Nicholson C, Dean JM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Real-time free cortisol quantification among critically ill children. Pediatr Crit Care Med. 2011 Sep;12(5):525-31. doi: 10.1097/PCC.0b013e3181fe4474. |
| 23506003 | Background | Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Berghe G. Reduced cortisol metabolism during critical illness. N Engl J Med. 2013 Apr 18;368(16):1477-88. doi: 10.1056/NEJMoa1214969. Epub 2013 Mar 19. |
| 12433670 | Background | Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003 Mar 1;167(5):695-701. doi: 10.1164/rccm.200207-682OC. Epub 2002 Nov 14. |
| 21705885 | Background | Wong HR, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Shanley TP, Bigham MT, Wheeler DS, Doughty LA, Tegtmeyer K, Poynter SE, Kaplan JM, Chima RS, Stalets E, Basu RK, Varisco BM, Barr FE. Validation of a gene expression-based subclassification strategy for pediatric septic shock. Crit Care Med. 2011 Nov;39(11):2511-7. doi: 10.1097/CCM.0b013e3182257675. |
| 23547046 | Background | McNally JD, Doherty DR, Lawson ML, Al-Dirbashi OY, Chakraborty P, Ramsay T, Menon K. The relationship between vitamin D status and adrenal insufficiency in critically ill children. J Clin Endocrinol Metab. 2013 May;98(5):E877-81. doi: 10.1210/jc.2013-1126. Epub 2013 Apr 1. |
| 27153945 | Derived | O'Hearn K, McNally D, Choong K, Acharya A, Wong HR, Lawson M, Ramsay T, McIntyre L, Gilfoyle E, Tucci M, Wensley D, Gottesman R, Morrison G, Menon K; Canadian Critical Care Trials Group. Steroids in fluid and/or vasoactive infusion dependent pediatric shock: study protocol for a randomized controlled trial. Trials. 2016 May 6;17(1):238. doi: 10.1186/s13063-016-1365-6. |
| Nurse declined to give study drug |
|
| BG001 | Placebo | Patients randomized to the placebo arm will receive a placebo solution consisting of normal saline equivalent in volume to the appropriate dose of hydrocortisone. Hydrocortisone and placebo will be identical in appearance, volume and smell as hydrocortisone is made up in normal saline and dissolves completely with no visible precipitate. The dosing regimen will be identical to the hydrocortisone arm. Placebo: The placebo (normal saline) will be identical in appearance, volume and smell to the active study drug (hydrocortisone). |
| BG002 | Total | Total of all reporting groups |
| Months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
|
|
| Secondary | 1a. Time to Administration of the First Dose of Study Drug | This objective is a measure of protocol adherence. The goal is to have patients randomized within 6 hours, and study drug administration completed within 8 hours of starting a vasoactive medication. We will consider adherence to our protocol to be adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | This feasibility objective, as stated a priori in the protocol, was analyzed for the full study cohort and was not compared between arms. Objective 1a was to determine the time to administration of the first dose of study drug for the full cohort. | Posted | Mean | Standard Deviation | hours | 8 hours from starting vasoactive medication |
|
|
|
| Secondary | 1b. Weaning of Study Drug to q8h When Patient is Hemodynamically Stable | This objective is a measure of protocol adherence. The goal is weaning of study drug to q8h within 12 hours of no escalation of therapy. We will consider adherence to our protocol to be adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | The percentage of study drug doses administered correctly was calculated for the full cohort.This feasibility objective was analyzed for the full cohort, and as stated a prior in our protocol, was not compared between study arms. | Posted | Number | % of doses administered correctly | 7 days |
|
|
|
| Secondary | 1c. Discontinuation of Study Drug When Off All Vasoactive Medications | This objective is a measure of protocol adherence. The goal is to discontinue study drug within 12 to 18 hours of vasoactive medications being stopped. We will consider adherence to the protocol adequate if secondary outcomes 1a to 1c are met in 80% of enrolled patients. | The percentage of study drug doses that were administered correctly for the full cohort.This feasibility objective, as stated a priori in the protocol, was analyzed for the full study cohort and was not compared between arms. | Posted | Number | % of doses administered correctly | 7 days |
|
|
|
| Secondary | Number of Patients Started on Open Label Steroids by the Treating Physician | We will consider the number of patients started on open label steroids by the treating physician to be acceptable if it occurs in less than 10% of patients. We will also collect information on the clinical parameters of patients when open label steroids are given. | The total number (and %) of patients in the full cohort who were administered open-label steroids by the treating physician.This feasibility objective, as stated a priori in the protocol, was not compared or reported separately by study arm. | Posted | Count of Participants | Participants | 7 days |
|
|
|
| Secondary | Time to Discontinuation of Vasoactive Infusions | The time to discontinuation of vasoactive agents will be used to better estimate the sample size for the full study. | Posted | Median | Inter-Quartile Range | hours | Daily during hospital admission (up to 28 days) |
|
|
|
| Secondary | Number of Participants With Incidence of Adverse Events and Mortality in the Full Cohort | The specific adverse events that will be measured include: severe bleeding, secondary infections and the use of insulin infusions. The incidence of adverse events and mortality rate was measured in aggregate (i.e. the whole cohort) in order to provide a better baseline estimate of these outcomes in our study population. | The number of participants with incidence of adverse events and mortality rate in the full cohort in order to provide a better baseline estimate of these outcomes in our study population. | Posted | Count of Participants | Participants | Daily during hospital admission (up to 28 days) |
|
|
|
| Secondary | Percentage of Patients for Whom Blood Samples Are Sent, and Successfully Received and Analyzed in Their Respective Labs | A total of 3 ml of blood in a red top tube will be collected within 24 hours of hospital admission. Patients with access for blood sampling and for whom consent has been obtained will have blood samples collected. The samples will be separated at each centre, stored until the end of the recruitment period, and then shipped to the principal investigators's centre as per the specific test requirements. The free cortisol and stratification biomarker samples will be batched and then shipped to Cincinnati for analysis at the end of the study. The number of samples collected, and the number of samples successfully received and analyzed at the principal investigator's site and at the Cincinnati lab will be determined at the end of the recruitment phase. | The total number of patients in the full cohort for whom a study blod sample was collected, received and analyzed. This feasibility outcome, as stated a priori in the study protocol, was analyzed for the full cohort and was not compared between arms. | Posted | Count of Participants | Participants | End of the study recruitment phase (up to 1.5 years) |
|
|
|
| 1 |
| 23 |
| 0 |
| 23 |
| 12 |
| 23 |
| EG001 | Placebo | Patients randomized to the placebo arm will receive a placebo solution consisting of normal saline equivalent in volume to the appropriate dose of hydrocortisone. Hydrocortisone and placebo will be identical in appearance, volume and smell as hydrocortisone is made up in normal saline and dissolves completely with no visible precipitate. The dosing regimen will be identical to the hydrocortisone arm. Placebo: The placebo (normal saline) will be identical in appearance, volume and smell to the active study drug (hydrocortisone). | 3 | 26 | 0 | 26 | 8 | 26 |
| New infection | Infections and infestations | Systematic Assessment |
|
| Insulin infusion | Endocrine disorders | Systematic Assessment |
|
Not provided
Not provided
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |