Phase 2 Double-blind, Randomized, Placebo Controlled Clinical Trial for the Prevention of Oral Mucositis Using Sub-microbial Doses of Doxycycline Hyclate in Patients With Acute Leukemia Receiving Induction Chemotherapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Complete response
研究概览
简要总结
Background. Mucositis is a complication of chemotherapy with no effective treatment. Aim.To evaluate the efficacy of sub-microbial doses of doxycycline hyclate in preventing the development of oral mucositis in patients with acute leukemia (AL) treated with induction chemotherapy.
Hypothesis. Doxycycline hyclate administration in sub-microbial dosage will reduce the incidence of oral mucositis in patients with AL who receive induction chemotherapy.
Methods. Double-blind, randomized, placebo-controlled clinical trial. At the Cancer National Institute (INCan), adult patients (> 18 years of age) with acute leukemia of recent diagnosis, scheduled to receive induction chemotherapy will be enrolled in the study. Written informed consent from the patients will be obtained preceding inclusion in the study.
At baseline and 3-times per week, during 21-days, patients will have an oral examination performed using the Oral Mucositis Assessment Scale (OMAS), oral pain, difficulty to swallow, and salivary flow measurements will be recorded.
A sample size of 164 subjects has been calculated, 74 subjects in each arm of the study. The primary end point of this study to evaluate the efficacy will be the proportion of patients treated with doxycycline or placebo without oral lesions associated with OM, during the 21 days of follow-up. Efficacy will be evaluated if the proportion of complete response (CR) is significantly higher than the proportion of events in the placebo group. Additional secondary endpoints will be the partial resolution of the oral lesions, the incidence of infections and the mortality in the study groups during the 21 days of follow-up. Results will be analyzed by using Chi-squared test and Wilcoxon-Mann-Whitney rank sum test.
详细描述
Background. Mucositis is a complication of chemotherapy with no effective treatment.
Aim.To evaluate the efficacy of sub-microbial doses of doxycycline hyclate in preventing the development of oral mucositis in patients with acute leukemia (AL) treated with induction chemotherapy.
Hypothesis. Doxycycline hyclate administration in sub-microbial dosage will reduce the incidence of oral mucositis in patients with AL who receive induction chemotherapy.
Methods. Double-blind, randomized, placebo-controlled clinical trial. At the Cancer National Institute (INCan), adult patients (> 18 years of age) with acute leukemia of recent diagnosis, scheduled to receive induction chemotherapy will be enrolled in the study. Written informed consent from the patients will be obtained preceding inclusion in the study.
Stratification according to the type of acute leukemia (myeloblastic and lymphoblastic) will be done. Random number tables will be used with balance for every four subjects; coded boxes will be utilized to preserve double blinding. Patients will be randomly assigned to receive either a sub-microbial dose of doxycycline hyclate or placebo (50 mg per day), immediately before the initiation of induction chemotherapy and daily during the following 21 days after chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 patients (> 18 years of age) with acute leukemia of recent diagnosis,scheduled to receive induction chemotherapy.
- •Capacity to give written informed consent.
- •Ability to attend the follow-up visits.
排除标准
- •Patients with allergy or intolerance to tetracyclines
- •Patients with acute or chronic renal insufficiency (basal blood creatinine >1.9 mg/dl)
- •Patients with the contraindication for the oral administration of drugs.
- •Patients with active septic processes or considered resolved in less than 7 days before the start of chemotherapy.
- •Patients who required tetracycline administration in the 28 days previous to randomization.
- •Adult patients with acute leukemia schedule to undergo stem-cell transplantation in the following two weeks.
- •Adult patients with hematological cancer with previous radiotherapy that may affect the salivary glands.
- •Inability to authorize a written informed consent.
- •Exclusion criteria
- •Patients who start chemotherapy before 12 hours of the assigned treatment.
- •Patients who have received less than 10 doses (5 days) of the assigned treatment.
- •Requirement to receive ergot derivates.
- •Patients who require the administration of acitretin/isotretinoin/tretinoin
- •Patients that receive photosensitive drugs during the study period (hydroxyquinone/retinoids or methoxsalen)
研究组 & 干预措施
doxycycline hyclate
Patients will be randomly assigned to receive either a sub-microbial dose of doxycycline hyclate or placebo (50 mg per day), immediately before the initiation of induction chemotherapy and daily during the following 21 days after chemotherapy.
干预措施: Doxycycline hyclate (Drug)
结局指标
主要结局
Complete response
时间窗: At baseline and 3-times per week, during 21-days after chemotherapy.
Complete response will be evaluated through the OMAS score.
次要结局
- Partial resolution of oral lesions, incidence of infections and mortality.(At baseline and 3-times per week, during 21-days after chemotherapy.)