Controling Intestinal Colonization of High Risk Patients With Extended Spectrum ß-Lactamase Producing Enterobacteriaceae (ESBL-E) - A Randomized Trial (CLEAR)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Short-term intestinal eradication
研究概览
简要总结
Rapid and rational health-care interventions are of great importance to efficiently combat the emergence of resistant and virulent bacteria. In recent years, spread of ESBL-E on a global level has been observed.
For ESBL-E, effective eradication regimens are not yet available. The current study therefore aims to assess a new approach to ESBL-E eradication. To avoid administration of the eradication regimen to patients at low risk of subsequent BSI with ESBL-E, the study population will be restricted to immunocompromised high-risk patients.
详细描述
Bloodstream infections (BSI) with multi-drug resistant (MDR) bacteria such as extended- spectrum betalactamase producing Enterobacteriaceae (ESBL-E) are associated with significant morbidity and mortality, particularly in the immunocompromised patient. In recent years, rapid spread of ESBL-E on a global level has been observed. While guidelines on effective infection control and treatment measures are urgently needed, the required basis of evidence is yet to be generated. Particularly data from interventional trials is lacking.
From October 2011 to December 2012, a multicenter cohort study on ESBL-E colonization and infection in haematology/oncology patients has been conducted within the Deutsches Zentrum für Infektionsforschung (DZIF) and allowed for a detailed description of the epidemiology of ESBL-E in this patient population. Based on these results, the sample size calculations for this study were carried out.
Rapid and rational health-care interventions are of great importance to efficiently combat the emergence of resistant and virulent bacteria. In recent years, spread of ESBL-E on a global level has been observed.
In 2012, the KRINKO (Kommission für Krankenhaushygiene und Infektionsprävention) at the Robert Koch Institute in Berlin, German, published their new recommendations on the management of colonization and infection with Gram-negative MDR bacteria, including ESBL-E. In high-risk settings, e.g. haematology/oncology wards and intensive care units, contact isolation is recommended for all patients who are colonized or infected with ESBL-E. While recommendations of the KRINKO are not legally binding, many institutions are now integrating these suggestions into their standards of care, given the recent increase in the prevalence of ESBL-E. This development is putting a considerable strain on patients and treating physicians. Firstly, previous studies have demonstrated the negative impact of long-term isolation on the patients' frequency of contacts with health care workers, a decrease in scores for self-esteem and an increase in scores for anxiety and depression.Secondly, proper contact isolation requires treatment in a single room. Many hospitals are, however, not equipped with sufficient numbers of single rooms, to accommodate all patients carrying MDR bacteria. Apart from problems associated with contact isolation, immunocompromised patients who are colonized with ESBL-E are at an increased risk of subsequent bloodstream infections (BSI).
Medical care providers are used to be faced with similar problems when dealing with methicillin-resistant Staphylococcus aureus (MRSA). However, nowadays, eradication regimens offer the possibility to remove MRSA from the skin and mucosa of colonized patients, thus interrupting its further spread to a considerable extent. For ESBL-E, effective eradication regimens are not yet available. The current study therefore aims to assess a new approach to ESBL-E eradication. To avoid administration of the eradication regimen to patients at low risk of subsequent BSI with ESBL-E, the study population will be restricted to immunocompromised high-risk patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Fecal colonization with ESBL-E, as confirmed by a positive sample (rectal swab or stool sample) obtained within 14 days prior to study enrolment
- •Ongoing or scheduled immunosuppression:
- •allogeneic or autologous hematopoietic stem cell transplantation within 14 days after enrollment or
- •chemotherapy with an expected duration of chemotherapy-associated neutropenia of at least 7 days within 14 days after enrollment or
- •solid organ transplantation within 14 days after enrollment or
- •administration of high-dose corticosteroids or other immunosuppressants for acute rejection of a solid organ transplant or for graft versus host disease after stem cell transplantation
- •Age of at least 18 years
- •Subject is not legally incapacitated
- •Written informed consent from the trial subject has been obtained
排除标准
- •Current or scheduled administration of ESBL-E active antibiotic treatment after receipt of the most recent sample showing intestinal ESBL-E colonization and within 10 days after randomization
- •Planned selective digestive tract decolonization within 42 days following randomization
- •Known hypersensitivity or allergy to any of the components of the study treatment
- •Moderate or severe liver dysfunction at baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN
- •Serum creatinine > 2 x the upper limit of the ULN
- •Inability to take oral medication
- •Concurrent participation in another clinical trial with an investigational drug is not permitted, unless the drug under study is related to the treatment of the underlying condition or a transplantation
- •Current pregnancy or nursing period
- •In female study participants, failure to use highly-effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:
- •Oral hormonal contraception ('pill')
- •Dermal hormonal contraception
- •Vaginal hormonal contraception (NuvaRing®)
- •Contraceptive plaster
- •Long-acting injectable contraceptives
- •Implants that release progesterone (Implanon®)
- •Tubal ligation (female sterilization)
- •Intrauterine devices that release hormones (hormone spiral)
- •Double barrier methods This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).
- •Patient has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the patient participating in the study, would make it unlikely for the patient to complete the study, or would confound the results of the study
- •Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
- •Persons held in an institution by legal or official order
研究组 & 干预措施
ESBL eradication regimen
Fosfomycin-trometamol (3 g granules dissolved in 200 ml of water for oral administration every 72h) and colistin (2x106 IU oral solution dissolved in 50-100 ml of water given orally every 6 hours) and gentamicin (an 80 mg oral solution dissolved in 50-100 ml of water given orally every 6 hours) will be administered in a double-blind fashion for a total duration of 7 days (day 1-7). The placebo treatment will be identical in taste, consistency, colour and packaging. To include the oral cavity into the eradication regimen, all medications should be gargled for at least 10 seconds before being swallowed.
干预措施: ESBL eradication regimen (Drug)
Placebo ESBL eradication
Placebo preparations of fosfomycin, gentamicin and colisitin, identical in taste, texture and color will be administered at the same rate as the active comparator medication.
干预措施: Placebo ESBL eradication (Drug)
结局指标
主要结局
Short-term intestinal eradication
时间窗: 11 days
Short-term intestinal eradication, defined as a fecal sample , negative for ESBL-E on day 6+/-1 and day 11+/-2
次要结局
- Emerging presence of non-ESBL multi-drug resistant bacteria(42 days)
- Intestinal microbiome(42 days)
- Quantitative assessment of intestinal ESBL-E burden(42 days)
- Long-term non-intestinal eradication d42(42 days)
- Long-term intestinal eradication d28(28 days)
- Short-term non-intestinal eradication(11 days)
- Long-term intestinal eradication d42(42 days)
- Long-term non-intestinal eradication d28(28 days)
- Incidence and severity of AEs(42 days)
- Rate of AE-related study drug discontinuations(42 days)
研究者
Maria J.G.T. Vehreschild
Dr. med.
University of Cologne