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InfluenzaPhase 1/2NCT00867139

TCAD vs. Monotherapy for Influenza A in Immunocompromised Patients

A Phase 1/2 study testing TCAD, Zanamivir or Oseltamivir and Open label treatment with TCAD in people with Influenza, run by Fred Hutchinson Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 1 year and older
Conditions the study is for
Influenza
What is being tested?
TCAD, Zanamivir or Oseltamivir and Open label treatment with TCAD
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesUnited States
Study dates
Mar 2009to Jan 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Inclusion criteria for randomized arms (both needed):
  • Age ≥7 years, male or female; AND
  • Influenza infection (i.e. upper respiratory tract infection)
  • 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
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  • Older age (≥ 7 years), with no asthma; AND
  • moderate to severe influenza; AND/OR
  • failure in randomized study monotherapy arm iii. Inclusion criteria for all subjects:
  • 1. Able to provide informed consent, or for whom consent may be provided by guardian 2. Immunocompromised, as defined by one of the following:
  • Recent hematopoietic cell transplantation (HCT) (within 2 years, all conditioning regimens, allogeneic, autologous, syngeneic; after 2 years patients with chronic graft-versus-host disease (GVHD) requiring systemic treatment may be included) or solid organ transplantation
  • Patients taking at least 2 immunosuppressants
  • Patients undergoing combination chemotherapy within the past 3 month 3. One or more of the following:
  • Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) taken orally.
  • presence of at least one constitutional symptom (headache, myalgia, malaise, or fatigue) of any severity (mild, moderate, or severe),
  • presence of at least one respiratory symptoms (e.g. cough, or sore throat) of any severity (mild, moderate, or severe),
  • other flu-like symptoms, where the clinician orders a respiratory virus test including influenza A or B 4. Positive test for influenza A (if available) 5. Onset of illness no more than 5 days prior to diagnosis. 6. Females patients of child-bearing age who are capable of conception (i.e. previously have not undergone surgical sterilization) must meet the following criteria:
  • Have been sexually abstinent or have used contraceptive agents (oral contraceptive or other hormonal contraceptives including vaginal rings or transdermal patches, intrauterine device (IUD), or barrier methods including condoms) during the 4 weeks prior to date of screening (3 months prior to enrollment for oral/hormonal contraceptives)
  • Agree to be sexually abstinent or use contraceptive agents (oral contraceptive or other hormonal contraceptives including vaginal rings or transdermal patches, intrauterine device (IUD), or barrier methods including condoms) from the date of screening through 24 weeks after the last dose of study drug

Who cannot join

  • Nausea that prevents taking oral medications
  • Use of antiviral influenza medication within 10 days(unless switched from randomized to open-label TCAD). An exception to this exclusion criterion may be made by site investigators for patients admitted after hours who receive one or two initial doses of antiviral influenza medication prior to enrollment.
  • Creatinine clearance (estimated by serum creatinine) less than 30 ml/min
  • Current clinical evidence of a recognized or suspected uncontrolled non-influenza infectious illness with onset prior to screening
  • Known hypersensitivity to amantadine, ribavirin, oseltamivir or zanamivir
  • Women who are pregnant (positive serum or urine pregnancy test), who are attempting to become pregnant, or who are breast-feeding
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  • Psychiatric or cognitive illness, or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect patient safety and/or compliance
  • Uncontrolled seizure disorder or history of a seizure activity within 12 months prior to study participation
  • Any significant finding in the patient's medical history or physical exam on Day 1 that, in the opinion of the investigator, would affect patient safety or compliance with the dosing schedule
  • Documented Influenza B viral co-infection

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Seattle Children's

    Seattle, Washington, 98105

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Pilot, Randomized Study Comparing the Safety, Tolerability and Pharmacokinetics of Combination Therapy (Amantadine, Ribavirin, Oseltamivir) Versus Neuraminidase Inhibitor Monotherapy to Influenza Virus Infected Immunocompromised Patients

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

Conditions
Influenza
Being tested
TCAD, Zanamivir or Oseltamivir, Open label treatment with TCAD
Keywords
Influenza, Immunocompromised, Antiviral
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TCADDrug

    Also called Symmetrel, Rebetol, Tamiflu

    TCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate)

  • Zanamivir or OseltamivirDrug

    Also called Relenza, Tamiflu

    Zanamivir or Oseltamivir

  • Open label treatment with TCADOther

    Also called Symmetrel, Rebetol, Tamiflu

    TCAD(amantadine hydrocholoride, ribavirin and oseltamivir phosphate)

Study groups in NCT00867139
Study groupRoleWhat they receive
TCAD-Randomized ArmExperimentalTCAD (amantadine hydrocholoride, ribavirin and oseltamivir phosphate)
Receives: Drug: TCAD
Neuraminidase Monotherapy ArmActive comparatorZanamivir or Oseltamivir
Receives: Drug: Zanamivir or Oseltamivir
TCAD Open Label ArmOtherTCAD for subjects who cannot tolerate or are ineligible to receive zanamivir
Receives: Other: Open label treatment with TCAD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 30 days after the final dose of study drug

Secondary outcomes (11)

  1. 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.

    Measured: baseline and 28 days

  2. Number of Patients Not Shedding Virus at Day 5 +/-1 and Day 10 +/- 1

    Measured: 10 days

  3. 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.

    Measured: 28 days

  4. 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

    Measured: from baseline up to 28 days

  5. Frequency of Confirmed Pneumonia

    Measured: 58 days

  6. Duration of Hospitalization

    Measured: from baseline up to 58 days

  7. Days on Supplemental Oxygen

    Measured: 58 days

  8. Number of Participants With ICU Admissions

    The number of participants with ICU admissions was evaluated.

    Measured: baseline and up to 58 days

  9. Number of Participants With Intubations

    Measured: 58 days

  10. Number of Deaths

    Measured: 58 days

  11. 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.

    Measured: 5 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Mar 2009 (estimated)
  2. Study startMar 2009
  3. Primary completionAug 2009
  4. Study completionJan 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00867139
Sponsor's protocol ID
2323.00
Other IDs
6895
Status last verified
Aug 2013
First submitted
20 Mar 2009
Last updated
15 Aug 2013
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23264438

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TCAD, Zanamivir or Oseltamivir and Open label treatment with TCAD in people with Influenza, run by Fred Hutchinson Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs), Drug Specific AEs or AEs Resulting in Treatment Interruption (time frame: 30 days after the final dose of study drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00867139, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2013.

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