Efficiency of AV2 Antiviral Drug in the Treatment of Human Papillomavirus-associated Precancerous Lesions of the Uterine Cervix: a Randomized Clinical Trial in Kinshasa, Democratic Republic of the Congo
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 327
- 试验地点
- 1
- 主要终点
- Change of lesions
研究概览
简要总结
- Introduction Cervical cancer (CC) is a major public health problem in Low-income countries (LICs), particularly in the Democratic Republic of the Congo (DRC), where the estimated number of cases is 3839 per year. (WHO, 2010).
Persistent infection with Human Papillomavirus (HPV) is recognized as the necessary cause for the development of CC. Thus, CC is a disease that is easily preventable primarily by vaccination against HPV and secondarily through screening and treatment of precancerous lesions of the cervix.
In LICs, the high incidence of CC is due to both high rates of infection with HPV, a failure to initiate and sustain effective screening programs based on cytology and the non-availability of vaccination against HPV. These situations highlight the need to implement simple and inexpensive screening and treatment methods suitable for LICs. These methods include screening by visual inspection of the cervix after application of acetic acid (VIA) and treatment with a topical antiviral drug (AV2). 2. Aims
This study aims to:
- Evaluate the clinical efficacy of AV2 as a treatment for HPV-associated lesions of the uterine cervix;
- Identify HPV genotypes found in Kinshasa;
- Determine the cost-effectiveness of an algorithm combining screening by VIA and AV2 and that combining VIA and cryotherapy treatment;
- Methods After basic training of local health workers on VIA, on collection of cervical samples for HPV testing (quantitative Polymerase Chain reaction, qPCR) and liquid-based cytology (LBC) and on application of AV2, a screening and treatment program will be offered to women aged 25 and older who will give their informed consent.
All women with lesions on VIA will be randomized into one of two groups to receive either treatment by AV2 or placebo.
All women with lesions on VIA will be monitored and reviewed after two months and after six months for repeat tests (VIA and LBC for lesions, qPCR for viral load, conversion and reinfection rates).
详细描述
CHAPTER 1: INTRODUCTION 1.1. BACKGROUND Cervical cancer (CC) is the third most common cancer in women, and the seventh overall, with an estimated 530 000 new cases per year. More than 85% of the global burden occurs in low-income countries (LICs). It is responsible for 275 000 deaths per year, about 88% of which occurring in LICs. Overall, the mortality: incidence ratio is 52. (Ferlay et al, 2010).
The link between genital high-risk Human papillomavirus (HPV) infections and CC was first demonstrated in the early 1980s by Harold zur Hausen, a German virologist. (Gissmann, L et al, 1983) HPV infection may be transient or persistent. When it persists, HPV induces changes in cells of the cervix, precisely in the transformation zone. These changes constitute the precursor lesions of cervical cancer. These precursor lesions are either called precancerous lesions, dysplasia or cervical intraepithelial neoplasia (CIN). Left untreated, they can progress from mild (CIN1) to moderate (CIN 2) to severe (CIN 3) dysplasia, and then to cancer. It appears that dysplasia is asymptomatic and progresses to cancer over a prolonged period of time, usually 7 to 20 years.
CC is then a potentially preventable and curable cancer. It can be prevented by vaccination against HPV and by screening. The latter involves the detection and treatment of precursors lesions on asymptomatic women.
Several tests can be used for CC screening:
- Cytology (conventional or liquid-based) also called Pap test or Pap smear.
- Visual inspection of the cervix after application of 5% acetic acid or vinegar (VIA).
- HPV-DNA testing. In LIC, the method of screening with low-cost test such as VIA and treating women with positive result with such treatment as cryotherapy in one single visit is known as the "see-and-treat approach". This would minimize loss to follow up, delay in treatment and missed cases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Sexually-active women
- •Women with intact uterine cervix
- •Voluntary written informed consent to participate in the study
排除标准
- •Virgin women
- •Pregnant or breast-feeding women, and women in the post-partum period
- •Subject is already diagnosed with cervical cancer
- •Medical history of any severe diseases like hepatitis, renal or liver dysfunction, cardiovascular, gastrointestinal, malignant tumor, or psychiatric disorders etc., which might influence the assessments or conduct of the trial by the discretion of the investigator
- •Intake or application of antivirals or other prohibited concomitant medication within 30 days prior to application of AV2®, or patients who plan to take such drugs during the trial
- •Known or suspected allergic or adverse response to the investigational product AV2 or its components (olive oil or d-limonene)
- •Inability to follow the study protocol
研究组 & 干预措施
AV2
Drug: application of topical spray on the cervix one time (2 puffs) topical application of 100µl AV2 antiviral spray( natural essential oil components in equal volumes diluted 50% in olive oil)
干预措施: AV2 (Drug)
Placebo
Drug: application of topical spray on the cervix one time (2 puffs) topical spray of 100 µl on the cervix.
干预措施: Placebo (Drug)
结局指标
主要结局
Change of lesions
时间窗: 2 months
lesion size" on a scale of 0 - 1 - 2: 0 : for a lesion \< 5 mm 1. : for a lesion 5-15 mm or involving 2 quadrants of the cervix 2. : for a lesion \> 15 mm or involving 3-4 quadrants or endocervically undefined.
次要结局
- absence of HPV DNA(2 months)
- correlation between change of lesions and change in HPV DNA(2 months)
- Change in HPV viral particle load(6 months)
研究者
Jean-Pierre Van geertruyden
Prof
Universiteit Antwerpen