Open Label Phase-II Randomized Trial of Three Liposomal Amphotericin B Regimens as Induction Therapy for Disseminated Histoplasmosis in AIDS Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Clinical Response
研究概览
简要总结
Disseminated histoplasmosis (DH) is one of the major AIDS-defining infections responsible for high mortality rates in HIV-infected patients. Liposomal amphotericin B (L-AmB) is considered the therapy of choice for AIDS-associated histoplasmosis.However, many patients in Latin America are still treated with high doses of deoxycholate amphotericin B (d-AmB) for long periods. These regimens are associated with toxicity and thus reduced efficacy. Therefore, a better treatment strategy is necessary to improve the activity of this amphotericin B treatment. Treatment with a high dose of L-AmB for short periods (rather than standard doses for longer periods) is a promising approach considering that the antifungal effect of amphotericin B depends on peak concentrations. This randomized open-label Phase II study aims to determinate and to compare the activity and safety of three L-AmB regimens, as induction therapy for DH in AIDS patients.
详细描述
This is a prospective randomized non-comparative multicenter open label trial of induction therapy with LAmB for DH in AIDS patients, followed by oral therapy with itraconazole.
The sample size planned is 99 patients of both sexes, older than 18 years (33 patients per study arm), infected with HIV and with confirmed diagnosis for DH. This sample size considers 10% of dropout.
The study will be conducted in accordance with the Helsinki Declaration, as well as the Standards national and international Guidelines for Good Clinical Practices.
Eight research centres in Brazil will competitively recruit patients: Santa Casa de Misericórdia de Porto Alegre (Porto Alegre; Dr Alessandro C. Pasqualotto), Hospital de Clínicas de Porto Alegre (Porto Alegre; Dr Diego R. Falci), Hospital Nossa Senhora da Conceição (Porto Alegre; Dr Marineide Melo), Hospital de Doenças Tropicais (Goiânia; Dr Cassia S. de Miranda Godoy), Hospital São José de Doenças Infecciosas (Fortaleza; Dr Terezinha M. J. Silva Leitão), and Hospital Giselda Trigueiro (Natal, Dr Monica B. Bay), Hospital Universitário Osvaldo Cruz (Recife, Dr. Filipe Prohaska Batista) e Instituto de Infectologia Emília Ribas (São Paulo, Dr. José Ernesto Vidal Bermudez).
AIDS patients with DH will be randomized to one of three study arms:
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
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
- •Adult (> 18 years) HIV-infected hospitalized patients diagnosed with HD by the means of (i) urine Histoplasma positive antigen (IMMY® monoclonal antibody test); (ii) confirmation by classical mycological methods (microscopy, culture or histopathology); or (iii) Histoplasma positive qualitative polymerase chain reaction (PCR) in bronchoalveolar lavage samples, bone marrow aspirates or tissue samples.
- •Patients will be included despite of the use of antiretroviral therapy (ART).
- •Understanding and signed the Informed Consent Form.
排除标准
- •Patients with previous diagnosis of histoplasmosis.
- •Pregnant or lactating women.
- •Patients with renal insufficiency (serum creatinine and urea > 1.5x the upper limit of normal).
- •Abnormal aminotransferases (up to > 3x the upper limit of normal) and patients with a severe prior reaction to polyene antifungal.
- •Patients who have received more than one dose of a polyene antifungal in the last 48 hours.
- •Patients who refuse to participate in the study.
- •Patients diagnosed with histoplasmosis that affect the central nervous system.
- •Patients who, at the trial of the attending physician, are expected to die within 48 hours.
- •Patients diagnosed with tuberculosis.
- •Patients with any disease or condition that, in the opinion of the investigator, may interfere with the assessments or participation in the study.
- •Patients receiving drugs that cause significant (relative or absolute) drug interaction with Itraconazole.
研究组 & 干预措施
single dose of L-AmB
single IV dose of 10 mg/kg of L-AmB on day 1;
干预措施: single dose of L-AmB (Drug)
2 doses of L-AmB
IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3;
干预措施: 2 doses of L-AmB (Drug)
2 weeks of L-AmB
IV dose of 3 mg/kg of L-AmB for 2 weeks.
干预措施: 2 weeks of L-AmB (Drug)
结局指标
主要结局
Clinical Response
时间窗: day 14
Maximum daily temperature lower than 37.8 °C
次要结局
- Overall Mortality(day 14)
研究者
Alessandro Pasqualotto
Principal Investigator
Federal University of Health Science of Porto Alegre