Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Number of children enrolled in the study protocol
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
研究组 & 干预措施
Admission/Intravascular Volume Expansion
- Infusion of 40 mL/kg of 0.9% normal saline (NS) IV over 60 minutes
- 0.9% NS with 5% dextrose at 150% of standard maintenance volume
- 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
- Oral fluids ad lib along with strict input/output documentation
- Fluids will be restricted if: A) Anuria for 12 hours OR B) Evidence of fluid overload
- 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.
干预措施: D5-0.9%NS (Drug)
Outpatient Observation
- 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).
- Oral fluids (preferably electrolyte maintenance solutions) ad lib following ED discharge
- Additional health assessments as required
- 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
干预措施: Routine home oral rehydration (Drug)
结局指标
主要结局
Number of children enrolled in the study protocol
时间窗: 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.
次要结局
- The proportion of children enrolled in each study arm who develop adverse events(at the end of the 24 month study recruiting period)
- Retention(at the end of the 24 month study recruiting period)
- Time requirements(at the end of the 24 month study recruiting period)
- Child/family perspectives(at the end of the 24 month study recruiting period)
- compliance/adherence(at the end of the 24 month study recruiting period)
- data collection tool performance(at the end of the 24 month study recruiting period)
- Impact on clinical services(at the end of the 24 month study recruiting period)
- Cost(at the end of the 24 month study recruiting period)