Information source: Metropolitan Autonomous University
ClinicalTrials. gov processed this data on August 23, 2015
Status: Not yet recruiting
Sponsored by: Metropolitan Autonomous University
Official(s) and/or principal investigator(s):
Sergio Ponce de Leon, MD, Study Director, Affiliation: Instituto Nacional de Ciencias MГ©dicas y NutriciГіn
Overall contact:
Velia Ramirez-Amador, PhD, Phone: 5255 5483 7206, Email: veliaram1@gmail. com
Summary
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.
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Primary outcome: Complete response
Secondary outcome: Partial resolution of oral lesions, incidence of infections and mortality.
Detailed description: 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. At baseline and 3-times per week, during 21-days, patients will have an oral examination performed using the Oral Mucositis Assessment Scale (OMAS). Also oral pain and difficulty to swallow will be recorded using a visual analogue scale. Also in each visit, salivary flow measurements (Schirmer's test modified version) will be done. The OMAS system is a validated index that evaluates the severity of oral mucositis by measuring the degree of ulceration/pseudomembrane and erythema in nine sites of the oral mucosa (upper and lower lip, right and left inner cheek, right and left ventral and lateral tongue, floor of the mouth, soft palate/fauces and hard palate). At each site, erythema is evaluated using a 3-point scale (0=none, 1=mild/moderate, 2=severe), and ulceration/pseudomembrane formation is evaluated using a 4-point scale (0=none, 1=cumulative surface area 3 cm2). The value of OMAS will be obtained by summing the erythema and ulceration/pseudomembrane sub-scores at each site and then averaging these scores across the affected sites. In order to rule out oral candidosis (OC), definitive diagnosis of OC requires the identification of pseudohyphae in exfoliative cytology samples stained with periodic acid Schiff. Likewise, the clinical diagnosis of herpes simplex virus (HSV) induced oral lesions will be confirmed by the virus-infected cells demonstrated in cytologic smears stained with Papanicolaou, and/or a clinical response to systemic antiviral therapy with acyclovir. A sample size of 164 subjects has been calculated, 74 subjects in each arm of the study. This estimate is based in the incidence of OM that is higher than 40% in patients with AL, and considering its reduction to half (20%), assuming an alpha value of 0. 05 (one-sided) and a minimum statistical power of 0. 80. The efficacy primary end point of this study will be the proportion of patients treated with doxycycline or placebo without oral lesions associated with OM, in 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. Statistical analysis. Results will be analysed by using Chi-squared test and Wilcoxon-Mann-Whitney rank sum test.
Eligibility
Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.
Criteria: 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.
- 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)
Locations and Contacts
Velia Ramirez-Amador, PhD, Phone: 5255 5483 7206, Email: veliaram1@gmail. com Instituto Nacional de Cancerologia, Mexico City 140180, Mexico; Not yet recruiting
Juan R Labardini-Mendez, MD, Phone: 56 28 04 00, Ext: 152, Email: labardini_juan@yahoo. com. mx
Juan R Labardini-Mendez, MD, Principal Investigator Additional Information
RamГrez-Amador V, Anaya-Saavedra G, Crespo-SolГs E, Camacho EI, GonzГЎlez-RamГrez I, Ponce-de-LeГіn 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.
Starting date: May 2010
Last updated: March 15, 2010
Look for the gold standard: double-blind, placebo-controlled, randomized tests
The most reliable type of study — especially for clinical trials — is generally thought to be the randomized, placebo-controlled, double-blind study.
If you are looking at a clinical trial, a psychology study, or an animal study, and it hasn't been designed like this — and there isn't a good reason that it couldn't have been — then you might want to question the results.
Let's break down this terminology:
1) Randomized: This means that the participants in the study were randomly placed into the experimental group and the comparison group. This is important because if people get to choose, they might be more likely to pick one or the other because of some unexpected factor.
As a hypothetical example, maybe people who are more optimistic are more likely to want to try a new drug for anxiety rather than an old drug that's being used for comparison. And maybe optimism is linked to better outcomes for generalized anxiety disorder. The researchers could end up thinking that these people got better because of the drug when it was actually because they were innately going to do better anyway.
Similar problems can be introduced if researchers choose who goes into which category. That's why random is best.
2) Placebo-controlled: A controlled study has an appropriate comparison group, also called a control group. In medical studies, one comparison group usually gets a placebo — a fake intervention such as a sugar pill. This is in order to distinguish what the drug actually did from what a participant's psychological expectations did. (Placebo effects can be surprisingly strong — so strong that they can oftentimes relieve pain, among other health problems. And they've been getting stronger in recent decades, according to Steve Silberman's in-depth placebo story from Wired.)
A good placebo group should be as similar to the experimental group as possible. So, for example, if you were testing out a drug that's a large, red pill, you'd ideally want to give the people in your comparison placebo group a large, red pill that's the same in every way, but doesn't contain the drug. (Yes, even a pill's color and size can have a placebo effect.) Some studies go as far as to do sham surgeries. including anesthesia, incisions, stitches — the works.
3) Double-blind: A study is "blind" if the participants don't know whether they are in the experimental group or the control group. For example, you don't want someone knowing if she's received a real drug or a fake drug because her expectations could change the outcome of the study.
A study is "double-blind" if the researchers in personal contact with participants also don't know which treatment they are administering. You don't want the nurse giving out pills to know if they're real or not because then subtle differences in his behavior could influence patients — and therefore the results.
Card 6 of 9
No comments:
Post a Comment