SepsisPhase 2StePSNCT00732277
Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis - a Randomised Pilot Study
A Phase 2 study testing hydrocortisone in people with Sepsis, run by University Hospital Southampton NHS Foundation Trust at 3 sites in United Kingdom.
Trial summary
Severe bacterial infections affecting multiple body organs, called severe sepsis (including meningococcal sepsis), remain an important cause of death and disability among children. Read more about this study
- Who is it for?
- Ages 3 months to 14 years
- Conditions the study is for
- Sepsis
- What is being tested?
- hydrocortisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Apr 2008to Apr 2012
- Phase
- Phase 2
- 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 3 months to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Severe sepsis where enrolment can occur within 20 hours of first contact with paediatric intensive care, or within 20 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU. Randomisation should occur within 24 hours of first contact with paediatric intensive care, or within 24 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU.
- Requiring mechanical ventilation (The subjects must be mechanically ventilated for entry into the study but this is not time limited. It is routine practice at study centres to pre-emptively ventilate children with evolving sepsis)
Who cannot join
- Concomitant steroid therapy, vasopressor treatment >24 hrs or use of etomidate (not recommended for use in children less than 10 years and selectively inhibits 11 beta-hydroxylase)
- Patients who have a recognised indication for steroids
- Other immunosuppressive/immunomodulatory therapy (not including intravenous immunoglobulin which is considered standard therapy in toxic shock syndrome and may be given for this indication)
- Significant immunocompromise (eg HIV infection)
- Advanced malignancy
- Burns
Show all 14Show fewer
- Cardiopulmonary resuscitation
- Children not likely to survive the time period of the maximum study intervention (5 days)
- Patients who have undergone organ transplantation (including bone marrow transplantation)
- Patients undergoing plasma exchange or whole blood exchange transfusion
- Treatment with an investigational drug or device within the last 30 days prior to enrolment.
- Patients who have experienced a prior episode of infection or sepsis during the current hospitalisation.
- Patients who are pregnant (a pregnancy test will be carried out for females of 11 years and above as is standard practice for clinical trials).
- Immediate families of investigators or site personnel directly affiliated with the study. Immediate family is defined as child or sibling, whether biological or legally adopted.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Bristol Royal Hospital for Children
Bristol, UK, BS2 8BJ
Imperial College Healthcare NHS Trust
London, UK, W2 1NY
Southampton University Hospitals NHS Trust
Southampton, UK, SO16 6YD
About this study
Official title: Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis (Steroids in Paediatric Sepsis, StePS) - a Randomised Pilot Study
Severe bacterial infections affecting multiple body organs, called severe sepsis (including meningococcal sepsis), remain an important cause of death and disability among children. Although early recognition, powerful antibiotics, and good intensive care have improved outcome, we need new ways to further reduce the number of deaths. Research in adults has shown that steroid replacement therapy might be useful. However, children are known to respond differently to adults and a definitive trial in children is needed because of the potentially harmful as well as beneficial effects of steroids.
This pilot study will provide the necessary information to allow the rational design of a large trial conducted at multiple hospitals investigating the role of corticosteroid replacement therapy in childhood sepsis. The study will provide information on how to measure the effects of steroids, information on length of therapy and a better understanding of how steroids work in children. The results emerging from this study will ultimately allow paediatric intensive care clinicians to know whether or not steroids are safe and/or useful.
Read more
The primary objective of this open-label study is therefore to gather clinical and laboratory data with which to inform the design of a large phase 3 double blind randomised controlled trial (RCT). The study will provide basic limited safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints to be used in addition to mortality.
Definition of sepsis:
Presence of a documented infection (eg clinical evidence of pneumonia, skin or soft tissue infection, purpura fulminans, urinary tract infection, abdominal infection) or a diagnostic positive blood culture (community or hospital acquired) within the last 72 hours and at least two of the following, one of which must be abnormal temperature or leucocyte count[3] core temperature of >38.5°C or <36°C; tachycardia (mean heart rate >2 SD above normal for age); mean respiratory rate > 2 SD above normal for age; leucocyte count elevated or depressed for age.
Definition of severe sepsis:
Sepsis plus cardiovascular organ dysfunction (the need for at least 5mcg/kg/min dopamine or dobutamine, or any amount of adrenaline or noradrenaline support), acute respiratory distress syndrome (ARDS), or 2 or more other organ dysfunctions.
Read the detailed description
- PURPOSE: The Need for a Paediatric Trial of Steroids in Sepsis - potential benefits and risks Numerous targets for new therapies in sepsis have been identified, none of which have been shown to have been of benefit in children. The results of adult studies cannot therefore be extrapolated directly to childhood disease. Corticosteroids alter the inflammatory balance in both beneficial and harmful ways in severe sepsis. Recent adult studies have demonstrated transient adrenal insufficiency is associated with adverse outcome and that corticosteroids increase survival in specific patient groups, and steroid replacement has become a standard of care. There is little uniformity in the approach to steroid replacement therapy amongst leading paediatric centres in the UK. Expert opinion has emphasised that guidance is interim while awaiting appropriate paediatric studies. Steroids are perceived as "safe" and "cheap" but should not be introduced into paediatric practice without further research. Sepsis in childhood differs in terms of mortality (around 10% overall in children vs in excess of 40% in adults), background immunity, co-morbidity, and causative organisms. Given the lower overall mortality in childhood sepsis, steroids have the potential to disrupt the inflammatory balance in children causing greater harm than benefit. It is not known which patients should be targeted for therapeutic intervention; what are the most appropriate endpoints; whether the length of steroid therapy can be shorter in children; or whether immunological rebound will occur.
- DESIGN and METHODOLOGY:
This is an open randomised prospective pilot exploratory study of corticosteroid replacement therapy in three centres. Adrenal function measurements will be assessed on entry to the study. To investigate the inflammatory profile and the impact of corticosteroid replacement, blood will be taken for cytokine and coagulation protein analysis. This study will provide the pilot data necessary for the design of a definitive trial of corticosteroid replacement therapy with the identification of variables likely to improve our ability to stratify patients for intervention and the mechanistic characterisation of the modulatory effects of steroids on inflammation in children with severe sepsis. Enrolment will be undertaken in two stages (see flowsheet diagrams in protocol). Forty five eligible children will be randomly allocated to steroid replacement therapy for 2 days (n=30) or intensive investigation without intervention (n=15) in a 2:1 randomisation (stage 1); 45 subjects (stage 2) will then be randomly allocated to steroid replacement therapy for 5 days (n=30) or intensive investigation without intervention (n=15). Randomisation will the undertaken in accordance with a computer-generated list and will be stratified by age (<1 years; 1 year or more). Progression from stage 1 to stage 2 will follow an interim analysis by a Trial Monitoring Group to ensure safety. This escalating approach will provide safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints in addition to mortality, reducing the potential for adverse events in the pilot phase while providing data relevant to this population. A large excess of serious adverse events in stage 1 will result in study termination. After careful consideration by the investigators and during the peer review process, placebo will not be used in this study, which will inform a future large phase 3 randomised controlled trial.
RESEARCH PARTICIPANTS WILL RECEIVE THE FOLLOWING INTERVENTIONS THAT ARE NOT PART OF ROUTINE CLINICAL CARE (Please also refer to figures 1-4 in the protocol that we are unable to reproduce here): Children will be screened on admission to PICU. Entry into the study following consent involves a clinical test of endocrine function involving 2 blood tests. The list of procedures conducted in the study is as follows:
- confirm eligibility requirements, assess pre-existing conditions and medical history, record weight, height, vital signs, data to inform clinical severity scores, complete infection assessment, clinically relevant laboratory investigations
- corticotrophin stimulation test
- multiple study samples (endocrine, cytokine and coagulation tests)
- corticosteroid treatment if randomised to treatment group
- follow-up in routine clinic
- Conditions
- Sepsis
- Being tested
- hydrocortisone
- Keywords
- sepsis, septicaemia, septicemia, paediatric, pediatric, children
- Medical subject headings
- Sepsis, Toxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydrocortisoneDrug
Also called Solu-Cortef®, Hydrocortisone sodium succinate
Patients will be assigned to treatment with hydrocortisone at 100mg/m2/24 hours in 4 divided doses (25 mg/m2/q 6 hourly) for 8 doses (48 hours) in phase 1 of study (45 patients, 30 receive IMP) or 20 doses (120 hours) in phase 2 (45 patients, 30 receive IMP).
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients in this arm will be given the following IMP intraveneously at 6 hour intervals - hydrocortisone (100mg/m2/24 hours) Receives: Drug: hydrocortisone |
| Control | No intervention | in each phase of study 15 patients will receive no IMP as control arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
primary efficacy endpoint is all cause mortality
Measured: 28 days
primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes
Measured: 28 days
Secondary outcomes (11)
PIM2
Measured: entry
PELOD
Measured: daily to 28 days or PICU discharge
ICU mortality
Measured: 28 days
time until shock reversal, defined as cessation of inotropic support for 24 hours
Measured: 28 days
time to resolution of multiorgan dysfunction
Measured: 28 days
time to resolution of base deficit
Measured: 28 days
time to resolution of lactate
Measured: 28 days
time to decision to discharge from ICU
Measured: 28 days
laboratory analysis of adrenal function
Measured: 6 days and convalescence
laboratory analysis of inflammatory parameters (defined in protocol)
Measured: 6 days and convalescence
laboratory analysis of coagulation parameters (defined in protocol)
Measured: 6 days and convalescence
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2008 (estimated)
- Study startApr 2008
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (79)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, St Mary's NHS Trust, University of Bristol, University Hospitals Bristol and Weston NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Saul N Faust, MBBS PhD, Study chair, University of SouthamptonSimon Nadel, MB BS, Principal investigator, Imperial College LondonRobert S Heyderman, MBBS PhD, Study director, University of LiverpoolDiana M Gibb, MBChB MD, Study director, Medical Research CouncilMichael Levin, MBBCH PhD, Study director, Imperial College LondonAndrew Wolf, MBBChir MD, Principal investigator, Univeristy of BristolJohn V Pappachan, MB BChir, Study director, University Hospital Southampton NHS Foundation TrustSarah Walker, MA PhD, Study director, Medical Research Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00732277
- Sponsor's protocol ID
- RHM CHI 434
- Other IDs
- 2007-002788-28, 07/H0504/139
- Acronym
- StePS
- Status last verified
- May 2016
- First submitted
- 7 Aug 2008
- Last updated
- 6 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Aneja R, Carcillo JA. What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock? Arch Dis Child. 2007 Feb;92(2):165-9. doi: 10.1136/adc.2005.088450. Epub 2006 Sep 26.
PubMed 17003064Booy R, Habibi P, Nadel S, de Munter C, Britto J, Morrison A, Levin M; Meningococcal Research Group. Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Arch Dis Child. 2001 Nov;85(5):386-90. doi: 10.1136/adc.85.5.386.
PubMed 11668100Despond O, Proulx F, Carcillo JA, Lacroix J. Pediatric sepsis and multiple organ dysfunction syndrome. Curr Opin Pediatr. 2001 Jun;13(3):247-53. doi: 10.1097/00008480-200106000-00006.
PubMed 11389359Stoll BJ, Holman RC, Schuchat A. Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics. 1998 Aug;102(2):e18. doi: 10.1542/peds.102.2.e18.
PubMed 9685463Thorburn K, Baines P, Thomson A, Hart CA. Mortality in severe meningococcal disease. Arch Dis Child. 2001 Nov;85(5):382-5. doi: 10.1136/adc.85.5.382.
PubMed 11668098Watson 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.
PubMed 12433670Cohen J. The immunopathogenesis of sepsis. Nature. 2002 Dec 19-26;420(6917):885-91. doi: 10.1038/nature01326.
PubMed 12490963Boldrick JC, Alizadeh AA, Diehn M, Dudoit S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):972-7. doi: 10.1073/pnas.231625398.
PubMed 11805339Nau GJ, Richmond JF, Schlesinger A, Jennings EG, Lander ES, Young RA. Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1503-8. doi: 10.1073/pnas.022649799. Epub 2002 Jan 22.
PubMed 11805289Faust SN, Heyderman RS, Levin M. Disseminated intravascular coagulation and purpura fulminans secondary to infection. Baillieres Best Pract Res Clin Haematol. 2000 Jun;13(2):179-97. doi: 10.1053/beha.2000.0067.
PubMed 10942620Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997 Jul;112(1):235-43. doi: 10.1378/chest.112.1.235. No abstract available.
PubMed 9228382van Dissel JT, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet. 1998 Mar 28;351(9107):950-3. doi: 10.1016/S0140-6736(05)60606-X.
PubMed 9734942Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med. 1999 Jul;27(7):1230-51. doi: 10.1097/00003246-199907000-00002.
PubMed 10446814Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet. 1999 Mar 27;353(9158):1049-53. doi: 10.1016/s0140-6736(98)08350-0.
PubMed 10199352Nadel S, Newport MJ, Booy R, Levin M. Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease. J Infect Dis. 1996 Oct;174(4):878-80. doi: 10.1093/infdis/174.4.878.
PubMed 8843235
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Corticosteroid Therapy in Childhood Severe Sepsis (Steroids in Paediatric Sepsis, StePS) - a Randomised Pilot Study
- ClinicalTrials.gov ID
- NCT00732277
- Acronym / sponsor ID
- StePS / RHM CHI 434
- Conditions
- Sepsis
- Keywords
- sepsis, septicaemia, septicemia, paediatric, pediatric, children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Imperial College London, St Mary's NHS Trust, University of Bristol, University Hospitals Bristol and Weston NHS Foundation Trust
- Study start
- Apr 2008
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 11 Aug 2008 (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.
Severe bacterial infections affecting multiple body organs, called severe sepsis (including meningococcal sepsis), remain an important cause of death and disability among children. Although early recognition, powerful antibiotics, and good intensive care have improved outcome, we need new ways to further reduce the number of deaths. Research in adults has shown that steroid replacement therapy might be useful. However, children are known to respond differently to adults and a definitive trial in children is needed because of the potentially harmful as well as beneficial effects of steroids.
This pilot study will provide the necessary information to allow the rational design of a large trial conducted at multiple hospitals investigating the role of corticosteroid replacement therapy in childhood sepsis. The study will provide information on how to measure the effects of steroids, information on length of therapy and a better understanding of how steroids work in children. The results emerging from this study will ultimately allow paediatric intensive care clinicians to know whether or not steroids are safe and/or useful.
The primary objective of this open-label study is therefore to gather clinical and laboratory data with which to inform the design of a large phase 3 double blind randomised controlled trial (RCT). The study will provide basic limited safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints to be used in addition to mortality.
Definition of sepsis:
Presence of a documented infection (eg clinical evidence of pneumonia, skin or soft tissue infection, purpura fulminans, urinary tract infection, abdominal infection) or a diagnostic positive blood culture (community or hospital acquired) within the last 72 hours and at least two of the following, one of which must be abnormal temperature or leucocyte count[3] core temperature of >38.5°C or <36°C; tachycardia (mean heart rate >2 SD above normal for age); mean respiratory rate > 2 SD above normal for age; leucocyte count elevated or depressed for age.
Definition of severe sepsis:
Sepsis plus cardiovascular organ dysfunction (the need for at least 5mcg/kg/min dopamine or dobutamine, or any amount of adrenaline or noradrenaline support), acute respiratory distress syndrome (ARDS), or 2 or more other organ dysfunctions.
Detailed description
- PURPOSE: The Need for a Paediatric Trial of Steroids in Sepsis - potential benefits and risks Numerous targets for new therapies in sepsis have been identified, none of which have been shown to have been of benefit in children. The results of adult studies cannot therefore be extrapolated directly to childhood disease. Corticosteroids alter the inflammatory balance in both beneficial and harmful ways in severe sepsis. Recent adult studies have demonstrated transient adrenal insufficiency is associated with adverse outcome and that corticosteroids increase survival in specific patient groups, and steroid replacement has become a standard of care. There is little uniformity in the approach to steroid replacement therapy amongst leading paediatric centres in the UK. Expert opinion has emphasised that guidance is interim while awaiting appropriate paediatric studies. Steroids are perceived as "safe" and "cheap" but should not be introduced into paediatric practice without further research. Sepsis in childhood differs in terms of mortality (around 10% overall in children vs in excess of 40% in adults), background immunity, co-morbidity, and causative organisms. Given the lower overall mortality in childhood sepsis, steroids have the potential to disrupt the inflammatory balance in children causing greater harm than benefit. It is not known which patients should be targeted for therapeutic intervention; what are the most appropriate endpoints; whether the length of steroid therapy can be shorter in children; or whether immunological rebound will occur.
- DESIGN and METHODOLOGY:
This is an open randomised prospective pilot exploratory study of corticosteroid replacement therapy in three centres. Adrenal function measurements will be assessed on entry to the study. To investigate the inflammatory profile and the impact of corticosteroid replacement, blood will be taken for cytokine and coagulation protein analysis. This study will provide the pilot data necessary for the design of a definitive trial of corticosteroid replacement therapy with the identification of variables likely to improve our ability to stratify patients for intervention and the mechanistic characterisation of the modulatory effects of steroids on inflammation in children with severe sepsis. Enrolment will be undertaken in two stages (see flowsheet diagrams in protocol). Forty five eligible children will be randomly allocated to steroid replacement therapy for 2 days (n=30) or intensive investigation without intervention (n=15) in a 2:1 randomisation (stage 1); 45 subjects (stage 2) will then be randomly allocated to steroid replacement therapy for 5 days (n=30) or intensive investigation without intervention (n=15). Randomisation will the undertaken in accordance with a computer-generated list and will be stratified by age (<1 years; 1 year or more). Progression from stage 1 to stage 2 will follow an interim analysis by a Trial Monitoring Group to ensure safety. This escalating approach will provide safety data, information on length of therapy and an assessment of possible clinical and laboratory endpoints in addition to mortality, reducing the potential for adverse events in the pilot phase while providing data relevant to this population. A large excess of serious adverse events in stage 1 will result in study termination. After careful consideration by the investigators and during the peer review process, placebo will not be used in this study, which will inform a future large phase 3 randomised controlled trial.
RESEARCH PARTICIPANTS WILL RECEIVE THE FOLLOWING INTERVENTIONS THAT ARE NOT PART OF ROUTINE CLINICAL CARE (Please also refer to figures 1-4 in the protocol that we are unable to reproduce here): Children will be screened on admission to PICU. Entry into the study following consent involves a clinical test of endocrine function involving 2 blood tests. The list of procedures conducted in the study is as follows:
- confirm eligibility requirements, assess pre-existing conditions and medical history, record weight, height, vital signs, data to inform clinical severity scores, complete infection assessment, clinically relevant laboratory investigations
- corticotrophin stimulation test
- multiple study samples (endocrine, cytokine and coagulation tests)
- corticosteroid treatment if randomised to treatment group
- follow-up in routine clinic
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: hydrocortisonePatients in this arm will be given the following IMP intraveneously at 6 hour intervals - hydrocortisone (100mg/m2/24 hours) |
| Control | No intervention | –in each phase of study 15 patients will receive no IMP as control arm |
Who may qualify
- Ages
- 3 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Severe sepsis where enrolment can occur within 20 hours of first contact with paediatric intensive care, or within 20 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU. Randomisation should occur within 24 hours of first contact with paediatric intensive care, or within 24 hours of the diagnosis of severe sepsis when this diagnosis is made on PICU.
- Requiring mechanical ventilation (The subjects must be mechanically ventilated for entry into the study but this is not time limited. It is routine practice at study centres to pre-emptively ventilate children with evolving sepsis)
Key exclusion criteria (14 listed)
- Concomitant steroid therapy, vasopressor treatment >24 hrs or use of etomidate (not recommended for use in children less than 10 years and selectively inhibits 11 beta-hydroxylase)
- Patients who have a recognised indication for steroids
- Other immunosuppressive/immunomodulatory therapy (not including intravenous immunoglobulin which is considered standard therapy in toxic shock syndrome and may be given for this indication)
- Significant immunocompromise (eg HIV infection)
- Advanced malignancy
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 |
|---|---|---|
| hydrocortisoneAlso: Solu-Cortef®, Hydrocortisone sodium succinatePatients will be assigned to treatment with hydrocortisone at 100mg/m2/24 hours in 4 divided doses (25 mg/m2/q 6 hourly) for 8 doses (48 hours) in phase 1 of study (45 patients, 30 receive IMP) or 20 doses (120 hours) in phase 2 (45 patients, 30 receive IMP). | Drug | Treatment |
Primary outcome
primary efficacy endpoint is all cause mortality
Time frame: 28 days
primary toxicity endpoint is Serious Adverse Events, excluding sepsis-related events specified as secondary outcomes
Time frame: 28 days
11 secondary outcomes
PIM2
Time frame: entry
PELOD
Time frame: daily to 28 days or PICU discharge
ICU mortality
Time frame: 28 days
time until shock reversal, defined as cessation of inotropic support for 24 hours
Time frame: 28 days
time to resolution of multiorgan dysfunction
Time frame: 28 days
time to resolution of base deficit
Time frame: 28 days
time to resolution of lactate
Time frame: 28 days
time to decision to discharge from ICU
Time frame: 28 days
laboratory analysis of adrenal function
Time frame: 6 days and convalescence
laboratory analysis of inflammatory parameters (defined in protocol)
Time frame: 6 days and convalescence
laboratory analysis of coagulation parameters (defined in protocol)
Time frame: 6 days and convalescence
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 6 May 2016.
- Background: PubMed 17003064Aneja R, Carcillo JA. What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock? Arch Dis Child. 2007 Feb;92(2):165-9. doi: 10.1136/adc.2005.088450. Epub 2006 Sep 26.
- Background: PubMed 11668100Booy R, Habibi P, Nadel S, de Munter C, Britto J, Morrison A, Levin M; Meningococcal Research Group. Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery. Arch Dis Child. 2001 Nov;85(5):386-90. doi: 10.1136/adc.85.5.386.
- Background: PubMed 11389359Despond O, Proulx F, Carcillo JA, Lacroix J. Pediatric sepsis and multiple organ dysfunction syndrome. Curr Opin Pediatr. 2001 Jun;13(3):247-53. doi: 10.1097/00008480-200106000-00006.
- Background: PubMed 9685463Stoll BJ, Holman RC, Schuchat A. Decline in sepsis-associated neonatal and infant deaths in the United States, 1979 through 1994. Pediatrics. 1998 Aug;102(2):e18. doi: 10.1542/peds.102.2.e18.
- Background: PubMed 11668098Thorburn K, Baines P, Thomson A, Hart CA. Mortality in severe meningococcal disease. Arch Dis Child. 2001 Nov;85(5):382-5. doi: 10.1136/adc.85.5.382.
- Background: PubMed 12433670Watson 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.
- Background: PubMed 12490963Cohen J. The immunopathogenesis of sepsis. Nature. 2002 Dec 19-26;420(6917):885-91. doi: 10.1038/nature01326.
- Background: PubMed 11805339Boldrick JC, Alizadeh AA, Diehn M, Dudoit S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA. Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):972-7. doi: 10.1073/pnas.231625398.
- Background: PubMed 11805289Nau GJ, Richmond JF, Schlesinger A, Jennings EG, Lander ES, Young RA. Human macrophage activation programs induced by bacterial pathogens. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1503-8. doi: 10.1073/pnas.022649799. Epub 2002 Jan 22.
- Background: PubMed 10942620Faust SN, Heyderman RS, Levin M. Disseminated intravascular coagulation and purpura fulminans secondary to infection. Baillieres Best Pract Res Clin Haematol. 2000 Jun;13(2):179-97. doi: 10.1053/beha.2000.0067.
- Background: PubMed 9228382Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. 1997 Jul;112(1):235-43. doi: 10.1378/chest.112.1.235. No abstract available.
- Background: PubMed 9734942van Dissel JT, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet. 1998 Mar 28;351(9107):950-3. doi: 10.1016/S0140-6736(05)60606-X.
- UK NIHR Medicines For Children Research NetworkLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Sepsis, Septic Shock
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.
Saul N Faust, MBBS PhD study chair
University of Southampton
Simon Nadel, MB BS principal investigator
Imperial College London
Robert S Heyderman, MBBS PhD study director
University of Liverpool
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hydrocortisone in people with Sepsis, run by University Hospital Southampton NHS Foundation Trust at 3 sites in United Kingdom.
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 2 inclusion and 14 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 6 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
primary efficacy endpoint is all cause mortality (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT00732277, which also lists 79 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 6 May 2016.