Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

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追踪信息

首次提交日期 ^ICMJE

July 2, 2018

首次发布日期e ^ICMJE

October 5, 2018

最后更新发布日期

October 5, 2018

预计研究开始日期 ^ICMJE

September 17, 2017

预计主要完成日期

December 31, 2018 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Occurrence of Adverse Events[ Time Frame: From baseline to day 42 ]

Occurrence of Adverse Events over 42 days observation period

Occurrence of Severe Adverse Events[ Time Frame: From baseline to day 42 ]

Occurrence of Severe Adverse Events over 42 days observation period

Occurrence of Abnormal Physical Symptoms[ Time Frame: From baseline to day 42 ]

Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities) over 42 days observation period

Occurrence of Abnormal Laboratory Values[ Time Frame: From baseline to day 42 ]

Occurrence of Abnormal Laboratory Values over 42 days observation period

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Frequency of residual parasitemia: % of patients with >1000 parasites/ ul at day 3 and 28[ Time Frame: day 3 and day 28 ]
Parasitemia is determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis.
Frequency of fever and malaria symptoms[ Time Frame: day 3 and day 28 ]
Percentage of patients with fever or malaria symptoms observed at Phisical Visit at day 3 and 28.
Mean parasitemia in the control and investigational arms[ Time Frame: day 2 and day 5 ]
Mean parasitemia by assessing the parasite count in blood, using thin film, thick film and qPCR analysis, expressed as parasites / ul at day 2, 3 and 5 measured in the control and investigational arms
Parasite half-life measured at 12 and 24 hours[ Time Frame: from baseline to 24 hours post-treatment ]
Mean parasite clearance half-life calculated using parasitemia measured at baseline, 12 and 24 hours post-treatment

描述性信息

简略标题 ^ICMJE

Triple Antimalarial Combination to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

正式标题 ^ICMJE

Triple Antimalarial Combination (Imatinib-DHA-PPQ) to Accelerate the Parasite Clearance and to Prevent the Selection of Resistant Parasites

简要概况

The purpose of this study is to provide a new drug combination for a better treatment of P. falciparum for a faster parasite clearance and to counteract artemisinin resistance.

详细说明

According to WHO, resistance to artemisinin derivatives (ART) is emerging in many areas of the Greater Mekong Region as a delayed parasite clearance following a standard treatment by artemisinin combined therapy (ACT). Artemisinin resistance is often accompanied by the resistance to the partner drugs such as piperaquine (PPQ), mefloquine (MEF), amodiaquine (AQ) and lumefantrine (LF). The slow and incomplete clearance of parasites following ACT treatment is considered to permit the selection of resistant parasites. The availability of new, more efficient treatments accelerating the clearance of parasites is therefore needed to counteract the selection of ART resistant strains. Imatinib (IMA) has been demonstrated to increase the efficacy of ART in a synergic fashion. This positive effect is further potentiated by low concentrations of PPQ. IMA is active both on the intra-erythrocyte asexual forms and on gametocytes. It is therefore expected that the combination DHA-PPQ-IMA should lead to faster and radical clearance of the parasites, therefore reducing the frequency of healthy carriers and transmission.

研究类型 ^ICMJE

Interventional

研究阶段

Phase 2

研究设计 ^ICMJE

分配: Randomized
干预模型: Sequential Assignment
干预模型描述: interventional
盲法: Interventional
盲法描述:The research method will be a Phase 2 trial, 2 arms, randomized, open label (only the microscopist will be blinded), adaptive, dose de-escalation, trial conducted in adult male subjects with uncomplicated P.falciparum malaria. In all phases, patients will be treated by a triple combination IMA-DHA-PPQ (ARM 1) or by the standard DHA-PPQ treatment (ARM 2).
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: Imatinib
triple combination for the treatment of malaria
Drug: Dihydroartemisinin-piperaquine
standard malaria treatment

研究工具

Experimental: imatinib-Dihydroartemisinin-piperaquine
triple combination
Active Comparator: Dihydroartemisinin-piperaquine
standard of care

招募信息

招募状态 ^ICMJE

Recruiting

预计入组 ^ICMJE

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

December 31, 2019

预计主要完成日期

December 31, 2018 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: 1. Patients diagnosed with mild to moderate P. falciparum malaria 2. Adult male, age 18-55 years 3. Good health conditions other than malaria 4. The patient did not take anti-malarial drugs in the past 4 weeks Exclusion Criteria: 1. unable to provide Informed Consent or Patient History Form 2. symptoms and signs of severe or complicated malaria including: continuous high fever over 39 °C, confusion, convulsions 3. parasitemia<150.000 parasites /microliter 4. other neurological or psychiatric symptoms or disorders 5. abnormal bleeding 6. resting hearth rate lower than 60 and higher than 100 bpm 7. abnormal ECG, history of cardiac diseases 8. male adults with corrected QT intervals > 450ms 9. signs, symptoms and laboratory results of impairment of vital organs such as liver, lungs, kidney and cardiovascular system 10. hemoglobin < 9.0 gm/100ml 11. symptoms and signs of infection such as pneumonia, dengue fever, and other viral or bacterial infection. 12. patients with symptoms of gastrointestinal infections or any sign of malabsorption that may interfere with drug absorption 13. concomitant infection by plasmodium species other than P. falciparum 14. inability to meet daily with local doctor during period of clinical trial 15. concomitant medicines like: 1. medicines used to treat high cholesterol in the blood (such as atorvastatin, lovastatin, simvastatin); 2. medicines used to treat hypertension and heart problems (such as diltiazem, nifedipine, nitrendipine, verapamil, felodipine, amlodipine); 3. medicined used to treat HIV (antiretroviral medicines): protease inhibitors (such as amprenavir, atazanavir, indinavir, nelfinavir, ritonavir), non-nucleoside reverse transcriptase inhibitors (such as efavirenz, nevirapine); 4. medicines used to treat microbial infections (such as telithromycin, rifampicin, dapsone); 5. medicines used to help you fall asleep: benzodiazepines (such as midazolam, triazolam, diazepam, alprazolam), zaleplon, zolpidem; 6. medicines used to prevent/treat epileptic seizures: barbiturates (such as phenobarbital), carbamazepine or phenytoin; 7. medicines used after organ transplantation and in autoimmune diseases (such as cyclosporin, tacrolimus); 8. sex hormones, including those contained in hormonal contraceptives (such as gestodene, progesterone, estradiol), testosterone; - glucocorticoids (hydrocortisone, dexamethasone); - omeprazole (used to treat diseases related to gastric acid production); 9. paracetamol (used to treat pain and fever); 10. theophylline (used to improve bronchial air flow); 11. nefazodone (used to treat depression); 12. aprepitant (used to treat nausea);

性别

参与研究的性别:

Male

年龄

最小年龄：18 Years ，最大年龄：55 Years

接受健康的志愿者

没有

可入组国家 ^ICMJE

Vietnam

管理信息

数据检测委员会

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

责任方

，

研究赞助商 ^ICMJE

Nurex S.r.l.

合作者 ^ICMJE

研究员 ^ICMJE

Principal Investigator: Huynh D Chien, MD, PhD UNIVERSITY OF HUE, VIETNAM AND VINMEC DANANG INTERNATIONAL HOSPITAL, Hai Chau, Danang.
Principal Investigator: Francesco M Turrini, MD, PhD University of Turin, Italy

PRS 账户

验证日期

October 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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