| ID | Type | Description | Link |
|---|---|---|---|
| 6895 | Other Identifier | FHCRC/UW CC IRB |
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The purpose of this study is to assess the safety and tolerability of triple combination antiviral drug (TCAD) for use in immunocompromised patients with Influenza A infection, and to gain data on the effectiveness of TCAD
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TCAD-Randomized Arm | Experimental | TCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate) |
|
| Neuraminidase Monotherapy Arm | Active Comparator | Zanamivir or Oseltamivir |
|
| TCAD Open Label Arm | Other | TCAD for subjects who cannot tolerate or are ineligible to receive zanamivir |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TCAD | Drug | TCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption | Abnormal lab data or newly appeared symptoms & signs were considered as AEs. Examined lab data: Blood cell count (WBC, differential count, Red Blood Cell (RBC), Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), platelets), Chemistry (Cl, bicarbonate (HCO3), K, Na), Renal function test (BUN, Creatinine, Creatinine clearance), Liver function test (AST, Alanine aminotransferase(ALT), T.Bil, gamma-glutamyltransferase) | 30 days after the final dose of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Viral Load Decrease as a Function of Time | Viral loads were measured by quantitative Polymerase Chain Reaction (PCR) on day 1, 3, 5, 7, 9, 15, 20 and 28, if applicable. | baseline and 28 days |
| Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1 |
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Inclusion Criteria:
i. Inclusion criteria for randomized arms (both needed):
ii. Inclusion criteria for open-label arm (at least one criteria required):
Young age (1-6 years) with any influenza severity, proven or probable influenza A (H1N1)(H274Y); OR
History of asthma; OR
Older age (≥ 7 years), with no asthma; AND
1. Able to provide informed consent, or for whom consent may be provided by guardian 2. Immunocompromised, as defined by one of the following:
Exclusion Criteria(all subjects):
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| Name | Affiliation | Role |
|---|---|---|
| Michael Boeckh, MD | Fred Hutchinson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Seattle Children's | Seattle | Washington | 98105 | United States | ||
| Fred Hutchinson Cancer Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23264438 | Result | Seo S, Englund JA, Nguyen JT, Pukrittayakamee S, Lindegardh N, Tarning J, Tambyah PA, Renaud C, Went GT, de Jong MD, Boeckh MJ. Combination therapy with amantadine, oseltamivir and ribavirin for influenza A infection: safety and pharmacokinetics. Antivir Ther. 2013;18(3):377-86. doi: 10.3851/IMP2475. Epub 2012 Dec 21. |
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Patients were recruited from subjects who had a hematopoietic cell transplantation (HCT) within 2 years or combination chemotherapy within 3 months, those with chronic graft-versus-host disease (GVHD) requiring systemic treatment after 2 years post HCT, or with GVHD taking at least 2 immunosuppressive drugs between February - September, 2009
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| ID | Title | Description |
|---|---|---|
| FG000 | TCAD | This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic. |
| FG001 | Neuraminidase Inhibitor Monotherapy | This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic. |
| FG002 | Open-labeled TCAD | This substudy was a randomized study comparing a triple combination antiviral drug (TCAD) therapy and oseltamivir (OSL) monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TCAD | This substudy was a randomized study comparing TCAD therapy and OSL monotherapy in immunocompromised patients with upper respiratory tract infection due to influenza A who were over 7 years of age and who were not asthmatic. |
| BG001 | Neuraminidase Inhibitor Monotheraphy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption | Abnormal lab data or newly appeared symptoms & signs were considered as AEs. Examined lab data: Blood cell count (WBC, differential count, Red Blood Cell (RBC), Hemoglobin, Hematocrit, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), platelets), Chemistry (Cl, bicarbonate (HCO3), K, Na), Renal function test (BUN, Creatinine, Creatinine clearance), Liver function test (AST, Alanine aminotransferase(ALT), T.Bil, gamma-glutamyltransferase) | Posted | Number | number of participants with AEs | 30 days after the final dose of study drug |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TCAD | Eligible immunocompromised subjects( age>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute GVHD | Gastrointestinal disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute GVHD | Skin and subcutaneous tissue disorders |
Study was terminated. Limitations of this study include: small sample size pilot study; inability to enroll the projected number of patients for full analysis before the study was terminated.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Boeckh MD | FHCRC | 206 667 6706 | mboeckh@fhcrc.org |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| C038167 | thiazole-4-carboxamide adenine dinucleotide |
| D000547 | Amantadine |
| D012254 | Ribavirin |
| D053139 | Oseltamivir |
| D053243 | Zanamivir |
| ID | Term |
|---|---|
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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| Zanamivir or Oseltamivir | Drug | Zanamivir or Oseltamivir |
|
|
| Open label treatment with TCAD | Other | TCAD(amantadine hydrocholoride, ribavirin and oseltamivir phosphate) |
|
|
| 10 days |
| Number of Participants With Viral Resistance as a Function of Drug Exposure | Viral resistance was assessed within 28 days after drug administration by detecting resistance-conferring mutation genes and compared to the value at baseline. | 28 days |
| Duration of Symptoms | Calculated as the number of days (mean) any persistent symptom lasted per patient as listed below. overall health, short of breath, chills, cough, diarrhea, ear pain, fatigue, fever, headache, hoarseness, muscle ache, phlegm, runny nose, sinus congestion, sneezing, sore throat, watery eyes, wheezing | from baseline up to 28 days |
| Frequency of Confirmed Pneumonia | 58 days |
| Duration of Hospitalization | from baseline up to 58 days |
| Days on Supplemental Oxygen | 58 days |
| Number of Participants With ICU Admissions | The number of participants with ICU admissions was evaluated. | baseline and up to 58 days |
| Number of Participants With Intubations | 58 days |
| Number of Deaths | 58 days |
| Pharmacokinetics (AUC0-last) of TCAD | Only 5 patients had partial pharmacokinetic (PK) data available. Plasma concentration of oseltamivir was measured at several time points in one patient receiving neuraminidase inhibitor monotherapy. Plasma concentration of oseltamivir, amantadine, and ribavirin were measured at several time points in four patients receiving TCAD therapy. Area under the time-concentration curve up to the last measured time point (AUC0-last) was calculated from the plasma concentration-time profiles by non-compartmental analysis. | 5 days |
| Seattle |
| Washington |
| 98109 |
| United States |
Neuraminidase inhibitors include zanamivir and oseltamivir phosphate in this study. |
| BG002 | Open-Labeled TCAD | Subjects with moderate respiratory symptoms and/or influenza-related lower respiratory tract disease, subjects who could not tolerate zanamivir, and children aged 1-6 years received open-label TCAD. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Neuraminidase Inihibitor Monotherapy |
oseltamivir (50 mg); three times a day for 10 days |
| OG002 | Open-labeled TCAD | amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days |
|
|
| Secondary | Number of Participants With Viral Load Decrease as a Function of Time | Viral loads were measured by quantitative Polymerase Chain Reaction (PCR) on day 1, 3, 5, 7, 9, 15, 20 and 28, if applicable. | Three patients could not get viral load at baseline. | Posted | Number | number of participants | baseline and 28 days |
|
|
|
| Secondary | Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1 | Participants assessed for viral shedding were those with available baseline viral load data. | Posted | Number | participants | 10 days |
|
|
|
| Secondary | Number of Participants With Viral Resistance as a Function of Drug Exposure | Viral resistance was assessed within 28 days after drug administration by detecting resistance-conferring mutation genes and compared to the value at baseline. | One open-labeled patient withdrew on day 5. | Posted | Number | Number of participants | 28 days |
|
|
|
| Secondary | Duration of Symptoms | Calculated as the number of days (mean) any persistent symptom lasted per patient as listed below. overall health, short of breath, chills, cough, diarrhea, ear pain, fatigue, fever, headache, hoarseness, muscle ache, phlegm, runny nose, sinus congestion, sneezing, sore throat, watery eyes, wheezing | one open labeled patient withdrew on day 5. | Posted | Mean | Standard Deviation | days | from baseline up to 28 days |
|
|
|
| Secondary | Frequency of Confirmed Pneumonia | Posted | Number | participants | 58 days |
|
|
|
| Secondary | Duration of Hospitalization | One open-labeled patient withdrew the study on day 5 | Posted | Mean | Standard Deviation | days | from baseline up to 58 days |
|
|
|
| Secondary | Days on Supplemental Oxygen | One open-labeled TCAD patient withdrew on day 5. | Posted | Mean | Standard Deviation | days | 58 days |
|
|
|
| Secondary | Number of Participants With ICU Admissions | The number of participants with ICU admissions was evaluated. | Posted | Number | participants | baseline and up to 58 days |
|
|
|
| Secondary | Number of Participants With Intubations | Posted | Number | participants | 58 days |
|
|
|
| Secondary | Number of Deaths | Posted | Number | participants | 58 days |
|
|
|
| Secondary | Pharmacokinetics (AUC0-last) of TCAD | Only 5 patients had partial pharmacokinetic (PK) data available. Plasma concentration of oseltamivir was measured at several time points in one patient receiving neuraminidase inhibitor monotherapy. Plasma concentration of oseltamivir, amantadine, and ribavirin were measured at several time points in four patients receiving TCAD therapy. Area under the time-concentration curve up to the last measured time point (AUC0-last) was calculated from the plasma concentration-time profiles by non-compartmental analysis. | Posted | Mean | Standard Deviation | ng*hr/mL | 5 days |
|
|
|
| 1 |
| 2 |
| 1 |
| 2 |
| EG001 | Neuraminidase Inihibitor Monotherapy | Eligible immunocompromised subjects( age>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receive TCAD or neuraminidase inhibitor monotherapy. | 1 | 1 | 0 | 1 |
| EG002 | Open-labeled TCAD | Subjects with moderate respiratory symptoms and/or influenza-related lower respiratory tract disease, subjects who could not tolerate zanamivir, and children aged 1-6 years received. | 1 | 4 | 0 | 4 |
| ARDS | Respiratory, thoracic and mediastinal disorders |
|
| acute GVHD | Gastrointestinal disorders |
|
| tachycardia | Cardiac disorders |
|
| increased ALP and GGT | Hepatobiliary disorders |
|
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| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D009930 |
| Organic Chemicals |
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D000081 | Acetamides |
| D000577 | Amides |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006146 | Guanidines |
| D000578 | Amidines |
| D012794 | Sialic Acids |
| D009438 | Neuraminic Acids |
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D006880 | Hydroxy Acids |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000606 | Amino Sugars |
| D002241 | Carbohydrates |