Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension

Официальное название

A Randomised Controlled Trial of Continuing Immunoglobulin Therapy, or Stopping With or Without Prophylactic Antibiotics, on Infection Rate in Patients With Acquired Hypogammaglobulinemia Secondary to Haematological Malignancies.

Обзор

The aim of the study is to find out if patients with blood cancers receiving immunoglobulin (Ig) for the purpose of preventing infections can safety stop immunoglobulin after six months of therapy, and take oral antibiotics instead to prevent serious infections. Patients may be eligible to join this study if they are aged 18 years or above, have an acquired hypogammaglobulinaemia secondary to a haematological malignancy, and have been receiving intravenous or subcutaneous Ig for longer than 6 consecutive months. Participants will be randomised (allocated by chance) to one of three treatment groups, as follows: * Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to take every day (ARM A) * Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to keep at home to use as soon as symptoms of an infection develop (ARM B) * Continue receiving immunoglobulin (IVIg or SCIg) - this is the usual care group (ARM C) The duration of each treatment is for 12 months from study entry. Participants will be asked to attend a screening/baseline visit so that their treating clinician can assess their eligibility for the trial and collect baseline data. If eligible for the trial, participants will then be randomly allocated to one of the three treatment groups. Once randomised, active participation in the study will last for 13 months. During this period, participants will be asked to return to the hospital for a study visit every 3 months, with monthly telephone visits to check-in on your progress between each in-person visit. Participants will also be asked to complete a study diary, recording treatment compliance and signs/symptoms of infection experienced throughout the study period. Types of assessments and data collected will include: Medical history, demographics, physical examination, blood tests, stool sample, quality of life questionnaires, information about your general health, hospitalisations, medications and procedures. In order to assess and compare the cost-effectiveness of the treatment groups, the study team will also request authorisation from participants to access their Medicare Benefits Schedule (MBS), Pharmaceutical Benefits Scheme (PBS), and Australian Immunisation Register (AIR) data.

Вмешательства

• Препарат trimethoprim-sulfamethoxazole (co-trimoxazole)
  Doxycycline is an alternative for participants with hypersensitivity to co-trimoxazole.
• Препарат amoxycillin/clavulanic acid and ciprofloxacin
  clindamycin is an alternative to amoxycillin/clavulanic acid for participants with hypersensitivity to penicillin.
• Препарат Immunoglobulins
  Intravenous monthly immunoglobulin or subcutaneous weekly immunoglobulin

Первичные конечные точки

• Event-free survival (EFS), defined as time from randomisation until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause. [Срок оценки: 12 months following randomisation]

Вторичные конечные точки (12)

• Proportion of patients who develop at least 1 Grade 3 or higher infection(s) from randomisation to 12 months. [Срок оценки: 12 months following randomisation]
• Proportion of patients with one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months. [Срок оценки: 12 months following randomisation]
• Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months. Data collected from medical records will inform this outcome measure. [Срок оценки: 12 months following randomisation]
• Proportion of patients with one or more microbiologically documented bacterial infections. [Срок оценки: 12 months following randomisation]
• Number of microbiologically documented bacterial infections. [Срок оценки: 12 months following randomisation]
• Time free from hospitalisation and antimicrobials with therapeutic intent. [Срок оценки: 12 months following randomisation]
• Proportion of patients with one or more treatment-related adverse events [Срок оценки: 12 months following randomisation]
• Number of treatment-related adverse events. [Срок оценки: 12 months following randomisation]
• Proportion of patients with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated. [Срок оценки: 12 months following randomisation]
• Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated. [Срок оценки: 12 months following randomisation]
• Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months [Срок оценки: Randomisation and 3, 6, 9 and 12 months following randomisation.]
• Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months [Срок оценки: Randomisation and 3, 6, 9 and 12 months following randomisation.]

Критерии участия

Критерии включения

• Aged greater than or equal to 18 years of age
• Diagnosis of chronic lymphocytic leukaemia (CLL), multiple myeloma (MM) or non-Hodgkin lymphoma (NHL).
• Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for longer than 6 consecutive months.
• Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator.
• Life expectancy greater than 12 months.
• Able to give informed consent, and willing and able to comply with each of the treatment arms.

Критерии исключения

• Prior or planned allogeneic haematopoietic stem cell transplantation.
• Major infection (Grade 3 or higher) in preceding 3 months, and/or current active infection requiring antimicrobial treatment.
• Already receiving daily antibiotic prophylaxis for the purpose of preventing bacterial infection (Note: patients may receive antiviral, antifungal and Pneumocystis jirovecii pneumonia (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 less than 30 mL/min).
• Previous splenectomy.
• Previous participation in this trial.
• Treating team deems enrolment in the study is not in the best interests of the patient.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Австралия · 7 центров

• Canberra Hospital — Garran
• Concord Hospital — Concord
• Royal North Shore — St Leonards
• Monash Medical Centre — Clayton
• Austin Hospital — Heidelberg
• The Alfred Hospital — Melbourne
• Sunshine Hospital — St Albans

Идентификаторы

NCT: NCT05678621 · TRU-RLS-21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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