Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00867139
Recruitment Status : Completed
First Posted : March 23, 2009
Results First Posted : June 4, 2013
Last Update Posted : August 15, 2013
Sponsor:
Information provided by (Responsible Party):
Michael Boeckh, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Influenza
Interventions Drug: TCAD
Drug: Zanamivir or Oseltamivir
Other: Open label treatment with TCAD
Enrollment 7
Recruitment Details 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
Pre-assignment Details  
Arm/Group Title TCAD Neuraminidase Inhibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 2 1 4
Completed 2 1 3 [1]
Not Completed 0 0 1
[1]
One open-labeled patient withdrew on day 5.
Arm/Group Title TCAD Neuraminidase Inhibitor Monotheraphy Open-Labeled TCAD Total
Hide Arm/Group Description 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. Neuraminidase inhibitors include zanamivir and oseltamivir phosphate in this study. 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. Total of all reporting groups
Overall Number of Baseline Participants 2 1 4 7
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 1 participants 4 participants 7 participants
<=18 years
0
   0.0%
1
 100.0%
2
  50.0%
3
  42.9%
Between 18 and 65 years
1
  50.0%
0
   0.0%
2
  50.0%
3
  42.9%
>=65 years
1
  50.0%
0
   0.0%
0
   0.0%
1
  14.3%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2 participants 1 participants 4 participants 7 participants
59.5  (17.7) 17  (0) 29.5  (26.0) 36.3  (25.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 1 participants 4 participants 7 participants
Female
1
  50.0%
1
 100.0%
2
  50.0%
4
  57.1%
Male
1
  50.0%
0
   0.0%
2
  50.0%
3
  42.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 1 participants 4 participants 7 participants
2 1 4 7
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption
Hide Description

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)

Time Frame 30 days after the final dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
oseltamivir (50 mg); three times a day for 10 days
amantadine (75 mg), oseltamivir (50 mg), and ribavirin (200 mg); three times a day for 10 days
Overall Number of Participants Analyzed 2 1 4
Measure Type: Number
Unit of Measure: number of participants with AEs
1 1 1
2.Secondary Outcome
Title Number of Participants With Viral Load Decrease as a Function of Time
Hide Description Viral loads were measured by quantitative Polymerase Chain Reaction (PCR) on day 1, 3, 5, 7, 9, 15, 20 and 28, if applicable.
Time Frame baseline and 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Three patients could not get viral load at baseline.
Arm/Group Title TCAD Neuraminidase Inhibitor Monotherapy Open-label TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 1 3
Measure Type: Number
Unit of Measure: number of participants
0 2
3.Secondary Outcome
Title Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1
Hide Description [Not Specified]
Time Frame 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants assessed for viral shedding were those with available baseline viral load data.
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 0 1 3
Measure Type: Number
Unit of Measure: participants
Day 5 +/-1 0 0
Day 10 +/- 1 0 1
4.Secondary Outcome
Title Number of Participants With Viral Resistance as a Function of Drug Exposure
Hide Description Viral resistance was assessed within 28 days after drug administration by detecting resistance-conferring mutation genes and compared to the value at baseline.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
One open-labeled patient withdrew on day 5.
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 3
Measure Type: Number
Unit of Measure: Number of participants
0 1 0
5.Secondary Outcome
Title Duration of Symptoms
Hide Description

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

Time Frame from baseline up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
one open labeled patient withdrew on day 5.
Arm/Group Title TCAD Neuraminidase Inhibitor Monotherapy Open-label TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 3
Mean (Standard Deviation)
Unit of Measure: days
4.5  (6.4) 1 4.7  (3.8)
6.Secondary Outcome
Title Frequency of Confirmed Pneumonia
Hide Description [Not Specified]
Time Frame 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 4
Measure Type: Number
Unit of Measure: participants
0 0 1
7.Secondary Outcome
Title Duration of Hospitalization
Hide Description [Not Specified]
Time Frame from baseline up to 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
One open-labeled patient withdrew the study on day 5
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 3
Mean (Standard Deviation)
Unit of Measure: days
6  (8.5) 6 1  (1.7)
8.Secondary Outcome
Title Days on Supplemental Oxygen
Hide Description [Not Specified]
Time Frame 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
One open-labeled TCAD patient withdrew on day 5.
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 3
Mean (Standard Deviation)
Unit of Measure: days
2  (1.4) 0 0  (0)
9.Secondary Outcome
Title Number of Participants With ICU Admissions
Hide Description The number of participants with ICU admissions was evaluated.
Time Frame baseline and up to 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 4
Measure Type: Number
Unit of Measure: participants
0 0 1
10.Secondary Outcome
Title Number of Participants With Intubations
Hide Description [Not Specified]
Time Frame 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 2 1 4
Measure Type: Number
Unit of Measure: participants
0 0 1
11.Secondary Outcome
Title Number of Deaths
Hide Description [Not Specified]
Time Frame 58 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description:
Eligible immunocompromised subjects( age>6 years) positively diagnosed with influenza A who had mild respiratory symptoms were randomized to receiveTCAD or neuraminidase inhibitor 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.
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.
Overall Number of Participants Analyzed 2 1 4
Measure Type: Number
Unit of Measure: participants
0 0 0
12.Secondary Outcome
Title Pharmacokinetics (AUC0-last) of TCAD
Hide Description 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.
Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TCAD Neuraminidase Inhibitor Monotherapy Open-lable TCAD
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 1 1 3
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
304 1497 2487  (2770)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/2 (50.00%)      1/1 (100.00%)      1/4 (25.00%)    
Gastrointestinal disorders       
Acute GVHD  1/2 (50.00%)  1 1/1 (100.00%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
ARDS  0/2 (0.00%)  0 0/1 (0.00%)  0 1/4 (25.00%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TCAD Neuraminidase Inihibitor Monotherapy Open-labeled TCAD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/2 (50.00%)      0/1 (0.00%)      0/4 (0.00%)    
Cardiac disorders       
tachycardia  1/2 (50.00%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0
Gastrointestinal disorders       
acute GVHD  1/2 (50.00%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders       
increased ALP and GGT  1/2 (50.00%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders       
acute GVHD  1/2 (50.00%)  1 0/1 (0.00%)  0 0/4 (0.00%)  0
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.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Michael Boeckh MD
Organization: FHCRC
Phone: 206 667 6706
Responsible Party: Michael Boeckh, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00867139     History of Changes
Obsolete Identifiers: NCT00865800
Other Study ID Numbers: 2323.00
6895 ( Other Identifier: FHCRC/UW CC IRB )
First Submitted: March 20, 2009
First Posted: March 23, 2009
Results First Submitted: December 21, 2012
Results First Posted: June 4, 2013
Last Update Posted: August 15, 2013