Steroid Use in Pediatric Fluid and Vasoactive Infusion Dependent Shock - Pilot Study

NCT02044159 | Completed Phase 4 Results DMC

• 1 other identifier: STRIPES-Pilot
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Shock

Keywords

Hydrocortisone; Pediatrics; Adrenal Insufficiency

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• 1a. Time to Administration of the First Dose of Study Drug

  8 hours from starting vasoactive medication

• 1b. Weaning of Study Drug to q8h When Patient is Hemodynamically Stable

  7 days

• 1c. Discontinuation of Study Drug When Off All Vasoactive Medications

  7 days

• Number of Patients Started on Open Label Steroids by the Treating Physician

  7 days

• Time to Discontinuation of Vasoactive Infusions

  Daily during hospital admission (up to 28 days)

Study Arms (2)

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.

Drug: Hydrocortisone

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.

Other: Placebo

Interventions

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).

Also known as: SOLU-CORTEF

Hydrocortisone

Placebo OTHER

The placebo (normal saline) will be identical in appearance, volume and smell to the active study drug (hydrocortisone).

Also known as: Placebo (saline solution)

Placebo

Eligibility Criteria

• Age: 1 Day - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children newborn to 17 years
• On any dose of any vasoactive infusion for between 1 to 6 hours

You may not qualify if:

• Patients who have known or suspected hypothalamic, pituitary or adrenal disease
• Patients who are currently receiving steroids for the treatment of shock/suspected shock prior to randomization
• Patients who are expected to have treatment withdrawn
• Patients who are premature infants (\<38 weeks corrected gestational age)
• Patients who are pregnant
• Patients post cardiac surgery
• Patient who received their first dose of vasoactive infusion \>24 hours after PICU admission
• Patient who is no longer on vasoactive infusion at the time of study enrollment, and/or is expected to no longer be on vasoactive infusion at the time the first dose of study drug will be administered
• Patients for whom primary cardiogenic shock is strongly suspected
• Patients for whom spinal shock is strongly suspected
• Patients for whom hemorrhagic or hypovolemic shock is strongly suspected
• Patients who were previously enrolled in the STRIPES study
• Patients who receive a vasoactive agent for reasons not related to shock
• Physician refusal

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead
• Alberta Children's Hospital: collaborator
• British Columbia Children's Hospital: collaborator
• London Health Sciences Centre: collaborator
• St. Justine's Hospital: collaborator
• IWK Health Centre: collaborator
• Montreal Children's Hospital of the MUHC: collaborator

Study Sites (7)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H8L1, Canada

Location

Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

Location

Hospital St. Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (16)

• 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.

  PMID: 23628832 BACKGROUND

• 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.

  PMID: 23867428 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.

  PMID: 17332201 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.

  PMID: 21897156 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.

  PMID: 23361625 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.

  PMID: 20299532 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.

  PMID: 20721535 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.

  PMID: 19352620 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.

  PMID: 15084695 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.

  PMID: 8706448 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.

  PMID: 21057361 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.

  PMID: 23506003 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.

  PMID: 12433670 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.

  PMID: 21705885 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.

  PMID: 23547046 BACKGROUND

• 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.

  PMID: 27153945 DERIVED

MeSH Terms

Conditions

Shock; Adrenal Insufficiency

Interventions

Hydrocortisone; hydrocortisone hemisuccinate; Saline Solution

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Katie O'Hearn, Research Coordinator
• Organization: Children's Hospital of Eastern Ontario

kohearn@cheo.on.ca

613-737-7600

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Investigator, CHEO Research Institute; Associate Professor, University of Ottawa; Physician, Division of Critical Care

Study Record Dates

• First Submitted: January 21, 2014
• First Posted: January 23, 2014
• Study Start: July 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: March 26, 2019
• Results First Posted: March 14, 2019

Record last verified: 2019-03

Locations

CA (7)