Hematological Malignancies
Conditions
Keywords
Hematological Malignancies, Respiratory Infection, Respiratory Syncytial Virus, RSV, Ribavirin, Virazole
Brief summary
Primary Objectives: 1. To determine whether aerosolized ribavirin is effective when given at an intermittent dose over 3 hours every 8 hours for therapy of RSV upper respiratory tract infection (URI) and whether it can prevent progression to pneumonia. 2. To determine the effect of this regimen on persistence of viral shedding.
Detailed description
Ribavirin is the drug that is normally given to treat upper respiratory infections caused by RSV. The drug is only effective when inhaled as an aerosol. This treatment requires the patient to be in a tent and inhale the medication. The usual method for administering this drug has been to inhale the medication continuously over 18 hours. In this study, the same total dose of the medication will be used, however, treatment will be for 3 hours every 8 hours. As part of your standard care, before treatment you will have blood drawn (around 2 teaspoons) for routine blood tests. You will have a washing from your throat and nose collected. For this procedure, around 1 teaspoon of saline will be sprayed into each nostril and you will blow your nose into a cup. You will have a swab of the nose and throat. You will also have a chest x-ray to check on the status of the disease. Women who are able to have children must have a negative blood or urine pregnancy test. Before treatment, you will be randomly assigned (as in the toss of a coin) to one of two groups. Participants in one group will receive treatment with ribavirin over 3 hours every 8 hours. Participants in the other group will receive treatment using the standard treatment schedule, ribavirin over 18 hours every 24 hours. For both groups, the drug will be administered as an aerosol using a face mask. This will require you to be in a tent while you are receiving therapy. Treatment will last between 5 and 10 days. This will require hospitalization. In addition to ribavirin treatment, you will also receive Xopenex inhalation therapy every 6 - 8 hours. Xopenex is a drug designed to make breathing easier. We may need to use another breathing treatment, albuterol inhalation therapy for one time if needed, directly after receiving ribavirin to make breathing easier. Every 2-4 days during treatment you will have blood collected (around 2 teaspoons) for routine tests. On Days 3 and 7 of treatment (+/- 2 days), you will have a repeat throat and nose washings/swabs. The washings and swabs will then be repeated once a week for 2 weeks, or until 2 consecutive cultures are negative, if that occurs sooner. If your doctor feels it is necessary, you may have a repeat chest x-ray. If at any time you develop signs of pneumonia, you will be removed from the study and will be treated with the standard schedule of ribavirin by continuous inhalation and/or other therapy for 18 hours a day. Also, if you develop any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. This is an investigational study. Ribavirin is FDA approved and is commercially available. However, the method of administration of ribavirin is investigational. Up to 50 patients will participate in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGRibavirin
Arm 1 = 6 Grams Over 18 hours Every 24 Hours
Sponsors
ICN Pharmaceuticals
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with these underlying malignancies will be eligible for this study: Autologous BMT patients, Allogeneic BMT patients, and patients with hematological malignancy. 2. Patients must be at least 5 years of age. 3. Only patients with infection limited to the URT will be eligible for entry on study 4. Patients will be eligible for entry on study if a nasopharyngeal wash or throat swab specimen is positive by rapid RSV antigen testing or by a positive culture for RSV.
Exclusion criteria
1. Patients with evidence of RSV LRTI as documented by a positive rapid RSV antigen testing or by a positive culture for RSV from a nasopharyngeal wash or throat swab AND new infiltrates on chest radiograph and/or abnormal blood gas determination 2. Patients with hypersensitivity to ribavirin or its components 3. Pregnant women. Participants must practice birth control during the study if they are sexually active. If the participant is pregnant, she may not be enrolled on this study. Mothers should refrain from breast-feeding during the study to avoid injury to their children. 4. Patients with positive RSV by rapid testing or culture in bronchoalveolar lavage regardless of the chest radiographic results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrences of Pneumonia | 6 Years | Treatment failure defined as progression to pneumonia within 7 days of initial treatment with aerosolized ribavirin. Patients considered as a failure or to have an unfavorable response if there develop signs and symptoms of pneumonia during therapy either evidenced by chest-xray or clinically, meaning they did reach the primary endpoint. |
Countries
United States
Participant flow
Recruitment details
Fifty patients were enrolled between October 2003 and March 2008, either from the outpatient settings or inpatients. Eligible patients were randomized to either Arm 1 (Standard regimen: 6gm over 18 hours every 24 hours) or Arm 2 (Modified regimen: 6gm over 3 hours every 8 hours).
Pre-assignment details
Only one patient was excluded from the trial after enrollment and before starting the intervention because his Chest X-Ray was read later on as positive for infiltrates.
Participants by arm
| Arm | Count |
|---|---|
| Standard Schedule - Ribavarin Aerosolized Ribavirin 6 gm over 18 hours every 24 hours | 18 |
| Modified Schedule - Ribavarin Aerosolized Ribavirin 6 gm over 3 hours every 8 hours | 32 |
| Total | 50 |
Baseline characteristics
| Characteristic | Modified Schedule - Ribavarin | Standard Schedule - Ribavarin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 17 Participants | 44 Participants |
| Age Continuous | 46.7 years STANDARD_DEVIATION 14.35 | 47.9 years STANDARD_DEVIATION 11.44 | 47.16 years STANDARD_DEVIATION 13.39 |
| Region of Enrollment United States | 32 participants | 18 participants | 50 participants |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 20 Participants | 9 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 32 |
| serious Total, serious adverse events | 2 / 18 | 4 / 32 |
Outcome results
Primary
Occurrences of Pneumonia
Treatment failure defined as progression to pneumonia within 7 days of initial treatment with aerosolized ribavirin. Patients considered as a failure or to have an unfavorable response if there develop signs and symptoms of pneumonia during therapy either evidenced by chest-xray or clinically, meaning they did reach the primary endpoint.
Time frame: 6 Years
Population: The analysis was carried out per protocol. All patients enrolled were included in the final analysis except one patient who was a screen failure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Schedule - Ribavarin | Occurrences of Pneumonia | 4 Participants |
| Modified Schedule - Ribavarin | Occurrences of Pneumonia | 3 Participants |