Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy (Stop-Ig)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 900
- 试验地点
- 3
- 主要终点
- Event-free survival (EFS).
研究概览
简要总结
This study is being conducted to find out how safe and effective different strategies of infection prevention are in comparison to each other, for preventing infection in patients with blood cancers. The best way to find out this information is to directly compare the effect of different treatment strategies in patients with blood cancers. We want to know how these different treatments impact on your health and your use of healthcare services.
This research project uses an Adaptive Platform Design. This design allows the researchers to compare multiple infection prevention strategies within the same trial at the same time (rather than running separate trials), to analyse results as the trial occurs and to add new research questions during the course of the trial.
The treatments that you may receive as part of the study will be determined by which domain(s) of the platform you participate in. By combining data collected within each domain as part of the platform, the researchers can investigate and compare treatment strategies and infection outcomes across a broader range of participants.
详细描述
This is a domain within the RATIONAL Platform Trial to test the effectiveness and safety of stopping Ig replacement with or without prophylactic antibiotics compare to continuing Ig replacement.
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
- None
盲法说明
An independent outcome adjudication committee will meet to review and adjudicate infection outcome data. These committee members will be blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for at least 6 consecutive months.
- •Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator.
- •Patient is willing and able to comply with each of the treatment arms.
排除标准
- •Prior or planned allogeneic haematopoietic stem cell transplantation.
- •Major infection (Grade 3 or higher) in preceding 3 months, and/or current active infection requiring systemic antimicrobial treatment.
- •Already receiving systemic antibiotic prophylaxis for the purpose of preventing bacterial infection (NB: patients may receive antiviral, antifungal and PJP prophylaxis).
- •Intolerance of all trial antibiotic options in either arm A or arm B.
- •Communication, compliance or logistical issues that are likely to limit patient's ability to take prophylactic or emergency antibiotics, or to obtain urgent medical attention for symptoms of infection.
- •Pregnant or breastfeeding.
- •Severe renal impairment (estimated or measured creatinine clearance of < 30 mL/min).
- •Previous splenectomy.
- •Previous participation in this domain.
- •Treating team deems enrolment in the domain is not in the best interests of the patient.
研究组 & 干预措施
Arm A: Stop Ig and commence prophylactic oral antibiotics
Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. NB: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.
干预措施: Trimethoprim Sulfamethoxazole (Drug)
Arm B: Stop Ig
Patients will be provided with amoxycillin/clavulanic acid 1750-2000mg/250mg and ciprofloxacin 750 mg to keep at home for initial use if symptoms of infection develop, with immediate review by their treating clinical team, or nearest emergency department or medical practitioner with phone contact to treating team if most practical.
NB: Clindamycin 600 mg is permitted as an alternative to amoxycillin/clavulanic acid for patients with hypersensitivity to penicillin. Ciprofloxacin is omitted for participants with hypersensitivity.
干预措施: Amoxycillin/clavulanic acid (Drug)
Arm C: Continue Ig
Participants will continue treatment with their current Ig replacement schedule. Participants will receive monthly (every 4 weeks ± 1 week) intravenous immunoglobulin at a dose of 0.4g/kg, modified to achieve an IgG trough level of at least lower limit of age-specific serum IgG reference range. For patients who have already had their Ig dose titrated to IgG trough level, they may continue on their current monthly dose of Ig replacement. SCIg, weekly, may be used in patients who meet local criteria for home-based self-administration in centres with established SCIg programs. Dosing is usually given at 100mg/kg/week, modified to achieve an IgG steady state level of at least the lower limit of the serum reference range.
干预措施: Immune Globulin Intravenous (Biological)
结局指标
主要结局
Event-free survival (EFS).
时间窗: 12 months following randomisation (or, in domains with a single treatment arm, time from registration).
Defined as time from randomisation (or, in domains with a single treatment arm, time from registration) until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause.
次要结局
- Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Occurrence of one or more microbiologically documented infections from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Number of microbiologically documented infections from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- All-cause mortality at 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Infection-related mortality at 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Time free from hospitalisation with antimicrobial administration with therapeutic intent from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Occurrence of one or more treatment-related adverse events.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Number of treatment-related adverse events.(12 months following randomisation (or, in domains with a single treatment arm, time from registration.)
- Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated from randomisation to 12 months.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)
- Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using different questionnaire.(Randomisation, Month 3, Month 6, Month 9 and Month 12.)
- Costs associated with allocated treatment arm and infections during study.(12 months following randomisation (or, in domains with a single treatment arm, time from registration).)