Efficacy in Scrub typhus of Combination therapy in Children versus Azithromycin or Doxycycline monotherapy: a double-blind Randomized control trial (ESCHAR Trial)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 649
- 试验地点
- 5
- 主要终点
- • The primary outcome will be a composite of all-cause mortality within 14 days, persistent
研究概览
简要总结
(i) Scrub typhus, caused by rickettsia Orientia tsutsugamushi, can lead to multi-organ dysfunction and high mortality. Doxycycline and azithromycin are the standard drug treatment available. Recent findings suggest that combination therapy may offer superior outcomes in adults. Keeping in mind antimicrobial stewardship, high-quality, clinical trials evaluating the efficacy and safety of this combination in children below 18 years are needed.
(ii) Novelty: To assess the comparative effectiveness of monotherapy versus combination therapy to determine whether combination therapy should become the standard-of-care for severe scrub typhus in children 1 month to 18 years.
(iii) Objectives:To compare combination therapy versus monotherapy for a composite outcome of all-
cause mortality within 14 days, persistent complications on day 7, and persistent fever (
more than 37.5°C) on day 5, amongst children 1 month to 18 years years presenting
with severe scrub typhus..
To compare all-cause 14-day mortality, fever resolution by day 5, organ dysfunction and
adverse effects profile between combination therapy vs. monotherapy in the above
defined population.
(iv) Methods:Study Design: A multi-center, double blind parallel arm, randomized control trial.
Study Population: Patients aged 1-month to18 years with severe scrub typhus and at least one organ involvement.
Intervention: Group 1: Doxycycline 4.5 mg/ kg/d in two divided doses for children less than 40 kg and 100 mg twice daily for children above 40 kg plus placebo, for 3 days after subsidence of fever or a total 7 days.
Group 2: Azithromycin 10 mg/kg/day in two divided doses plus placebo for 7 days. Group 3: Combination therapy (both drugs at the above dosages).
Outcome Measures:Primary outcome: will be a composite of all-cause mortality within 14 days,
persistent complications on day 7, and persistent fever ( more than 37.5°C ) on day 5.
Secondary outcome: 14-day all-cause mortality, fever defervescence at day 5, Time
to fever resolution, persistent complications at day 7, hospitalization stay, and adverse
events.
(v) Expected Outcome: The study will provide robust evidence on whether combination therapy vs. monotherapy reduces severe scrub typhus complications and mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 0.08 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •Participants eligible for inclusion in the trial if they meet all the following criteria: Children aged 1 month-18 years Suffering from scrub typhus (acute febrile illness of atleast 5 days) with a positive result on Scrub Typhus Rapid diagnostic test or presented with an eschar.
- •Atleast one organ -system involvement as per the Pediatric sequential organ failure assessment (pSOFA) scoring Fever of less than 5 days will be considered in case of co-presence of eschar or positive scrub RDT or IgM serology with cutoff optical density greater than or equal to 0.5 or a positive RT-PCR report.
排除标准
- •Participants will be excluded if they meet any of the following criteria: • Prior treatment with tetracyclines, macrolides, rifampicin or chloramphenicol for more than 24 hours within 48 hours before recruitment.
- •• Lethal congenital anomaly or known immundeficiency.
- •• History of hypersensitivity to macrolides or tetracylines • Denied consent.
结局指标
主要结局
• The primary outcome will be a composite of all-cause mortality within 14 days, persistent
时间窗: 14 days, day 7, day 5.
complications on day 7, and persistent fever ( more than 37.5°C) on day 5.
时间窗: 14 days, day 7, day 5.
次要结局
- Secondary outcome: will include 14-day all-cause mortality, fever defervescence at day 5, Time to fever resolution, persistent complications at day 7, hospitalization stay, and adverse events.(Day 5, Day 7 and Day 14)
研究者
Vidushi Mahajan
Government Medical College and Hospital Chandigarh