Hemolytic-Uremic SyndromePhase 1NCT03275792
Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion
A Phase 1 study testing D5-0.9%NS and Routine home oral rehydration in people with Hemolytic-Uremic Syndrome, run by University of Calgary at 1 site in Canada.
Trial summary
This study will provide feasibility data regarding the conduct of a clinical trail evaluating the use of early aggressive inpatient intravenous rehydration in children with Shiga Toxin producing E. coli infection. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Hemolytic-Uremic Syndrome
- What is being tested?
- D5-0.9%NS and Routine home oral rehydration
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- May 2020to Apr 2021
- Phase
- Phase 1
- 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age <18.0 years;
- STEC infection [positive culture OR antigen OR polymerase chain reaction test for Stx/gene];
- Day of illness 1-10: Children who develop HUS will do so by day #14 of illness;8 restricting enrolment to the first 10 days will ensure all participants are at risk of HUS.
Who cannot join
- Evidence of evolving HUS: A) Hematocrit <30% OR B) Platelet count <150 x 109/L;
- Responsible physician desires patient admission (therefore unable to randomize);
- Unable to contact family within 48 hours of positive stool test;
- Patient with history of atypical HUS;
- Chronic disease limiting fluid volumes administered (e.g. impaired cardiac function)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)
This study will provide feasibility data regarding the conduct of a clinical trail evaluating the use of early aggressive inpatient intravenous rehydration in children with Shiga Toxin producing E. coli infection.
Read the detailed description
Background: Shiga toxin-producing Escherichia coli (STEC) cause a spectrum of disease, ranging from asymptomatic carriage to bloody diarrhea and the hemolytic uremic syndrome (HUS). HUS is caused by a toxin that destroys red blood cells, consumes platelets and impairs kidney function. HUS results in morbidity and even death in otherwise healthy children. Over the last 30 years however, there has been extremely limited progress in preventing acute and long-term complications in children with STEC infection. However, it is believed that Shiga toxins generate clots or blockages in the kidneys that damage it much the way strokes cause brain damage. There is emerging evidence that if children with STEC infection are recognized early, then the interval between diarrhea onset and the presence of HUS could be exploited to preserve kidney function through the use of intravenous rehydration.
Study Design: The investigators propose to conduct the first randomized clinical trial of volume expansion therapy in children with STEC infection. Employing Alberta's unique province-wide microbiology network and its only two pediatric tertiary care centres, the investigators will conduct a proof of principal feasibility study that evaluates novel technologies to identify STEC infected children and those at risk for HUS.
Objectives: The primary outcome will be process: number of children recruited. Secondary outcomes will include: 1) resources: retention; refusal; compliance; eligibility criteria; questionnaires; data collection tools; and time requirements; 2) management: capacity and impact on clinical services; 3) scientific: utility of point-of-care STEC diagnostics; use of urine biomarkers to identify high risk children, monitoring of kidney injury and response to therapy; and safety.
Significance: This pilot will provide the necessary data to integrate novel technologies into the design and conduct of a multicentre, multinational, clinical trial that will reduce morbidity and mortality from STEC infection.
- Conditions
- Hemolytic-Uremic Syndrome
- Being tested
- D5-0.9%NS, Routine home oral rehydration
- Keywords
- Shiga-Toxigenic Escherichia coli, Child
- Medical subject headings
- Hemolytic-Uremic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D5-0.9%NSDrug
Admission for intravascular volume expansion
Routine home oral rehydrationDrug
Routine oral fluids as is given at home to all children with acute diarrheal disease
| Study group | Role | What they receive |
|---|---|---|
| Admission/Intravascular Volume Expansion | Experimental | 1. Infusion of 40 mL/kg of 0.9% normal saline (NS) IV over 60 minutes
2. 0.9% NS with 5% dextrose at 150% of standard maintenance volume
3. If urine output is <0.5 ml/kg/hr over a 12-hour period (AKI Stage 2), repeat 20 mL/kg bolus or boluses of 0.9% NS will be infused as long as there are no signs of central volume overload
4. Oral fluids ad lib along with strict input/output documentation
5. Fluids will be restricted if: A) Anuria for 12 hours OR B) Evidence of fluid overload
6. Daily laboratory tests and in-person assessment until inpatient discharge criteria reached:
A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child
7. Repeat hematocrit, platelet, renal function 24 and 72-hours post-discharge. Receives: Drug: D5-0.9%NS |
| Outpatient Observation | Active comparator | 1. Following standard emergency department (ED) care [volume status assessed; dehydration corrected employing oral rehydration in children with mild to moderate dehydration (most common); IV if severe (rarely)], children are discharged with saline lock IV (routine procedure across Canadian pediatric EDs).
2. Oral fluids (preferably electrolyte maintenance solutions) ad lib following ED discharge
3. Additional health assessments as required
4. Daily blood tests at a local laboratory with results conveyed daily to the site-investigator until outpatient discharge criteria achieved; no in-person assessment given logistics (i.e. distance), impact on family, and mirroring of standard practice A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child Receives: Drug: Routine home oral rehydration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of children enrolled in the study protocol
The number of children recruited per month per site will be calculated and will be related to the number screened, number eligible, and number consented.
Measured: at the end of the 24 month study recruiting period
Secondary outcomes (8)
The proportion of children enrolled in each study arm who develop adverse events
For participants enrolled in each study arm we will quantify the proportion that are admitted to Intensive Care Units, the proportion requiring respiratory support (CPAP, BiPAP, endotracheal intubation), hypoxia defined by the administration of supplemental oxygen, and evidence of congestive heart failure defined by blinded independent reviewers.
Measured: at the end of the 24 month study recruiting period
Retention
The proportion of children who complete the study protocol
Measured: at the end of the 24 month study recruiting period
Time requirements
We will quantify the number of hours children remain admitted and to which clinical units
Measured: at the end of the 24 month study recruiting period
Child/family perspectives
7-item likert scales will be employed to evaluate perspectives of parents and participants as appropriate related to study protocols, procedures and participation
Measured: at the end of the 24 month study recruiting period
compliance/adherence
The proportion of children enrolled in each study arm who comply with the key interventions of the respective study arms
Measured: at the end of the 24 month study recruiting period
data collection tool performance
Individual data fields will be audited with respect to data quality, reliability, completeness, timeliness of completion
Measured: at the end of the 24 month study recruiting period
Impact on clinical services
We will qualitatively explore with the department leads at the respective institutions if the study protocol had any impact on clinical care provided either to the admitted patients or to other patients on their services
Measured: at the end of the 24 month study recruiting period
Cost
We will quantify the costs per child in each study arm
Measured: at the end of the 24 month study recruiting period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study startMay 2020 (estimated)
- Primary completionApr 2021 (estimated)
- Study completionApr 2021 (estimated)
Why it stopped: Funding not obtained.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemolytic-Uremic SyndromeStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephen Freedman, MDCM, MSc, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275792
- Sponsor's protocol ID
- CHREB-12345
- Status last verified
- Sep 2019
- First submitted
- 29 Aug 2017
- Last updated
- 9 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Imdad A, Nelson JR, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2025 Apr 25;4(4):CD012997. doi: 10.1002/14651858.CD012997.pub3.
PubMed 40277027Imdad A, Mackoff SP, Urciuoli DM, Syed T, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD012997. doi: 10.1002/14651858.CD012997.pub2.
PubMed 34219224
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)
- ClinicalTrials.gov ID
- NCT03275792
- Acronym / sponsor ID
- CHREB-12345
- Conditions
- Hemolytic-Uremic Syndrome
- Keywords
- Shiga-Toxigenic Escherichia coli, Child
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding not obtained.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- May 2020 (estimated)
- Primary completion
- Apr 2021 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 8 Sep 2017 (actual)
- 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.
This study will provide feasibility data regarding the conduct of a clinical trail evaluating the use of early aggressive inpatient intravenous rehydration in children with Shiga Toxin producing E. coli infection.
Detailed description
Background: Shiga toxin-producing Escherichia coli (STEC) cause a spectrum of disease, ranging from asymptomatic carriage to bloody diarrhea and the hemolytic uremic syndrome (HUS). HUS is caused by a toxin that destroys red blood cells, consumes platelets and impairs kidney function. HUS results in morbidity and even death in otherwise healthy children. Over the last 30 years however, there has been extremely limited progress in preventing acute and long-term complications in children with STEC infection. However, it is believed that Shiga toxins generate clots or blockages in the kidneys that damage it much the way strokes cause brain damage. There is emerging evidence that if children with STEC infection are recognized early, then the interval between diarrhea onset and the presence of HUS could be exploited to preserve kidney function through the use of intravenous rehydration.
Study Design: The investigators propose to conduct the first randomized clinical trial of volume expansion therapy in children with STEC infection. Employing Alberta's unique province-wide microbiology network and its only two pediatric tertiary care centres, the investigators will conduct a proof of principal feasibility study that evaluates novel technologies to identify STEC infected children and those at risk for HUS.
Objectives: The primary outcome will be process: number of children recruited. Secondary outcomes will include: 1) resources: retention; refusal; compliance; eligibility criteria; questionnaires; data collection tools; and time requirements; 2) management: capacity and impact on clinical services; 3) scientific: utility of point-of-care STEC diagnostics; use of urine biomarkers to identify high risk children, monitoring of kidney injury and response to therapy; and safety.
Significance: This pilot will provide the necessary data to integrate novel technologies into the design and conduct of a multicentre, multinational, clinical trial that will reduce morbidity and mortality from STEC infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Admission/Intravascular Volume Expansion | Experimental | Drug: D5-0.9%NS1. Infusion of 40 mL/kg of 0.9% normal saline (NS) IV over 60 minutes 2. 0.9% NS with 5% dextrose at 150% of standard maintenance volume 3. If urine output is <0.5 ml/kg/hr over a 12-hour period (AKI Stage 2), repeat 20 mL/kg bolus or boluses of 0.9% NS will be infused as long as there are no signs of central volume overload 4. Oral fluids ad lib along with strict input/output documentation 5. Fluids will be restricted if: A) Anuria for 12 hours OR B) Evidence of fluid overload 6. Daily laboratory tests and in-person assessment until inpatient discharge criteria reached: A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child 7. Repeat hematocrit, platelet, renal function 24 and 72-hours post-discharge. |
| Outpatient Observation | Active comparator | Drug: Routine home oral rehydration1. Following standard emergency department (ED) care [volume status assessed; dehydration corrected employing oral rehydration in children with mild to moderate dehydration (most common); IV if severe (rarely)], children are discharged with saline lock IV (routine procedure across Canadian pediatric EDs). 2. Oral fluids (preferably electrolyte maintenance solutions) ad lib following ED discharge 3. Additional health assessments as required 4. Daily blood tests at a local laboratory with results conveyed daily to the site-investigator until outpatient discharge criteria achieved; no in-person assessment given logistics (i.e. distance), impact on family, and mirroring of standard practice A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age <18.0 years;
- STEC infection [positive culture OR antigen OR polymerase chain reaction test for Stx/gene];
- Day of illness 1-10: Children who develop HUS will do so by day #14 of illness;8 restricting enrolment to the first 10 days will ensure all participants are at risk of HUS.
Key exclusion criteria (5 listed)
- Evidence of evolving HUS: A) Hematocrit <30% OR B) Platelet count <150 x 109/L;
- Responsible physician desires patient admission (therefore unable to randomize);
- Unable to contact family within 48 hours of positive stool test;
- Patient with history of atypical HUS;
- Chronic disease limiting fluid volumes administered (e.g. impaired cardiac function)
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 |
|---|---|---|
| D5-0.9%NSAdmission for intravascular volume expansion | Drug | Admission/Intravascular Volume Expansion |
| Routine home oral rehydrationRoutine oral fluids as is given at home to all children with acute diarrheal disease | Drug | Outpatient Observation |
Primary outcome
Number of children enrolled in the study protocol
Time frame: at the end of the 24 month study recruiting period
The number of children recruited per month per site will be calculated and will be related to the number screened, number eligible, and number consented.
8 secondary outcomes
The proportion of children enrolled in each study arm who develop adverse events
Time frame: at the end of the 24 month study recruiting period
Retention
Time frame: at the end of the 24 month study recruiting period
Time requirements
Time frame: at the end of the 24 month study recruiting period
Child/family perspectives
Time frame: at the end of the 24 month study recruiting period
compliance/adherence
Time frame: at the end of the 24 month study recruiting period
data collection tool performance
Time frame: at the end of the 24 month study recruiting period
Impact on clinical services
Time frame: at the end of the 24 month study recruiting period
Cost
Time frame: at the end of the 24 month study recruiting period
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2020.
- Derived from this study: PubMed 40277027Imdad A, Nelson JR, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2025 Apr 25;4(4):CD012997. doi: 10.1002/14651858.CD012997.pub3.
- Derived from this study: PubMed 34219224Imdad A, Mackoff SP, Urciuoli DM, Syed T, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD012997. doi: 10.1002/14651858.CD012997.pub2.
- Individual participant dataSharing planned: Undecided
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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.
Stephen Freedman, MDCM, MSc principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing D5-0.9%NS and Routine home oral rehydration in people with Hemolytic-Uremic Syndrome, run by University of Calgary at 1 site in Canada.
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 3 inclusion and 5 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: withdrawn, as of the sponsor's last update on 9 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
Number of children enrolled in the study protocol (time frame: at the end of the 24 month study recruiting period). 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 NCT03275792, which also lists 2 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 9 Nov 2020.