A prospective, open-label, randomisation-controlled trial of combination antifungal therapy (Liposomal Amphotericin B and Posaconazole) vs single antifungal (Liposomal Amphotericin B) for initial treatment in Mucormycosis (ComPLiMenT Trial)
试验速览
- 阶段
- 2/3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Complete or partial response at week 3
研究概览
简要总结
Mucormycosis is caused by fungi of the order Mucorales. It is characterized by anangio-invasive disease leading to necrotizing arteritis of involved tissues. Itmost commonly affects immunocompromised patients. Untreatedmucormycosis is almost always fatal.
Even after more than one yearfollowing the origin of the pandemic, the pathogenesis of COVID19 remainspartially understood and understanding of the same continues to evolve withtime. As the highly infectious virus continues to give rise to new cases globally,one of the emerging concerns isserious upsurge in the number of cases of mucormycosis. It remains to be seen if thisincreasing incidence of mucormycosis in COVID19 is related to the illnessitself, the steroids and immunomodulators administered for treatment, or theworsening of underlying predisposing factors in the socio-economic upheavalcaused by the pandemic.
The management of mucormycosis includes acombination of surgical resection of affected tissues combined with antifungaltherapy. Polyenes (Amphotericin B) form the backbone of antifungal therapy inmucormycosis and have been the standard of care for so many years. In addition, newer agentssuch as Posaconazole (or isavuconazole) have been approved as salvage therapy. Unfortunately, despite adequate surgery and initial management with Amphotericin B, mortalityrates in cases of mucormycosis are remarkably high. Considering the pooroutcome, there is increasing interest in focusing on the role of combinationantifungal therapy in the treatment of mucormycosis. The ongoing COVID19 pandemicprovides us a grim scenario in terms of the number of cases of mucormycosis.However, the current situation also provides us with an opportunity to conduct aprospective clinical trial to evaluate the role of combination therapy ofpolyenes and azoles.
We intend to conductfollowing prospective, open-label,randomized control trial to evaluate the benefit of combination antifungaltherapy in the treatment of mucormycosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, variable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •All patients aged 18 years or more, newly diagnosed probable (clinical and radiological) or proven invasive mucormycosis will be included.
排除标准
- •1 Patients not willing to consent.
- •2 Patients with more than 5 days of primary antifungal therapy 3 Patients unable to receive enteral medications.
- •4 Co-existing conditions precluding the use of both Amphotericin B or Posaconazole a Liposomal Amphotericin B – history of hypersensitivity b Posaconazole – H/o hypersensitivity (other azoles), Concurrent drugs (Sirolimus: can result in sirolimus toxicity; CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of Torsades de Pointes; HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: can lead to rhabdomyolysis, Ergot alkaloids: can result in ergotism drug interactions); Transaminitis ( AST or ALT >5 times ULN) 5 Patients who are critically ill/ hemodynamic instability 6 Patients with active moderate and severe COVID19 illness at the time of recruitment 7 Breastfeeding/ pregnancy 8 Patient enrolled in other ongoing prospective drug trials for IM.
结局指标
主要结局
Complete or partial response at week 3
时间窗: 3 weeks
次要结局
- 1.Complete response at week 6 and week 12
- 2.Increased survival at week 12, 6 months and 12 months.
- 3.Reduction in all-cause mortality(12 months)