Intermittent Use of Aerosolized Ribavirin for Treatment of RSV
Study Details
Study Description
Brief Summary
Primary Objectives:
-
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.
-
To determine the effect of this regimen on persistence of viral shedding.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1: Standard Schedule - Ribavirin Aerosolized Ribavirin 6 grams over 18 hours every 24 hours |
Drug: Ribavirin
Arm 1 = 6 Grams Over 18 hours Every 24 Hours
Other Names:
|
| Experimental: 2: Modified Schedule - Ribavirin Aerosolized Ribavirin 2 grams over 3 hours every 8 hours |
Drug: Ribavirin
Arm 2 = 2 Grams Over 3 Hours Every 8 Hours.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with these underlying malignancies will be eligible for this study: Autologous BMT patients, Allogeneic BMT patients, and patients with hematological malignancy.
-
Patients must be at least 5 years of age.
-
Only patients with infection limited to the URT will be eligible for entry on study
-
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:
-
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
-
Patients with hypersensitivity to ribavirin or its components
-
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.
-
Patients with positive RSV by rapid testing or culture in bronchoalveolar lavage regardless of the chest radiographic results.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | U.T.M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- ICN Pharmaceuticals
Investigators
- Principal Investigator: Roy F. Chemaly, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ID03-0010
Study Results
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 Detail | 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. |
| Arm/Group Title | Standard Schedule - Ribavarin | Modified Schedule - Ribavarin |
|---|---|---|
| Arm/Group Description | Aerosolized Ribavirin 6 gm over 18 hours every 24 hours | Aerosolized Ribavirin 6 gm over 3 hours every 8 hours |
| Period Title: Overall Study | ||
| STARTED | 18 | 32 |
| COMPLETED | 18 | 32 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Standard Schedule - Ribavarin | Modified Schedule - Ribavarin | Total |
|---|---|---|---|
| Arm/Group Description | Aerosolized Ribavirin 6 gm over 18 hours every 24 hours | Aerosolized Ribavirin 6 gm over 3 hours every 8 hours | Total of all reporting groups |
| Overall Participants | 18 | 32 | 50 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
1
3.1%
|
1
2%
|
| Between 18 and 65 years |
17
94.4%
|
27
84.4%
|
44
88%
|
| >=65 years |
1
5.6%
|
4
12.5%
|
5
10%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
47.9
(11.44)
|
46.7
(14.35)
|
47.16
(13.39)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
9
50%
|
12
37.5%
|
21
42%
|
| Male |
9
50%
|
20
62.5%
|
29
58%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
18
100%
|
32
100%
|
50
100%
|
Outcome Measures
| Title | Occurrences of Pneumonia |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Standard Schedule - Ribavarin | Modified Schedule - Ribavarin |
|---|---|---|
| Arm/Group Description | Aerosolized Ribavirin 6 gm over 18 hours every 24 hours | Aerosolized Ribavirin 6 gm over 3 hours every 8 hours |
| Measure Participants | 18 | 32 |
| Number [Participants] |
4
22.2%
|
3
9.4%
|
Adverse Events
| Time Frame | 6 Years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Standard Schedule - Ribavarin | Modified Schedule - Ribavarin | ||
| Arm/Group Description | Aerosolized Ribavirin 6 gm over 18 hours every 24 hours | Aerosolized Ribavirin 6 gm over 3 hours every 8 hours | ||
All Cause Mortality |
||||
| Standard Schedule - Ribavarin | Modified Schedule - Ribavarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Standard Schedule - Ribavarin | Modified Schedule - Ribavarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/18 (11.1%) | 4/32 (12.5%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 0/18 (0%) | 0 | 1/32 (3.1%) | 1 |
| Anemia | 1/18 (5.6%) | 1 | 2/32 (6.3%) | 2 |
| Hyperglycemia | 0/18 (0%) | 0 | 1/32 (3.1%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhea | 1/18 (5.6%) | 1 | 4/32 (12.5%) | 6 |
| Hepatobiliary disorders | ||||
| Elevated Transaminase Level | 1/18 (5.6%) | 1 | 0/32 (0%) | 0 |
| Elevated Bilirubin level | 1/18 (5.6%) | 1 | 0/32 (0%) | 0 |
| Renal and urinary disorders | ||||
| Bladder Spasm | 0/18 (0%) | 0 | 1/32 (3.1%) | 1 |
| Elevated creatinine | 0/18 (0%) | 0 | 1/32 (3.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Acute Graft Versus Host Disease | 1/18 (5.6%) | 1 | 0/32 (0%) | 0 |
| Chronic Graft Versus Host Disease | 1/18 (5.6%) | 1 | 0/32 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Standard Schedule - Ribavarin | Modified Schedule - Ribavarin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/32 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Roy F Chemaly, MD/MPH, MBA /Associate Professor |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | 713-745-1116 |
| rfchemaly@mdanderson.org |
- ID03-0010