Mucositis | Double-blind-randomized,Placebo Controlled Trial for Chemotherapy-associated Oral Mucositis Using Doxycycline Hyclate
Mucositis research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: - 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. Exclusion Criteria: - 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)
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Doxycycline hyclateSub-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.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
doxycycline hyclatePatients 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.
Start Date: May 2010
Completed Date: February 2013
Phase: Phase 2
Primary Outcome: Complete response
Secondary Outcome: Partial resolution of oral lesions, incidence of infections and mortality.
Study sponsors, principal investigator, and references
Principal Investigator: Sergio Ponce de Leon, MD
Lead Sponsor: Metropolitan Autonomous University
Collaborator: Instituto Nacional de Cancerologia de Mexico
Ramírez-Amador V, Anaya-Saavedra G, Crespo-Solís E, Camacho EI, González-Ramírez I, Ponce-de-León S. Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy. Support Care Cancer. 2010 May;18(5):639-46. doi: 10.1007/s00520-009-0708-1. Epub 2009 Aug 6.