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Azithromycin in Patients With CF, Infected With Burkholderia Cepacia Complex

30. Juli 2009 aktualisiert von: Unity Health Toronto

Phase II, Randomized, Double Blind, Placebo-Controlled Trial of Azithromycin in Patients With CF, Chronically Infected With Burkholderia Cepacia Complex

Pulmonary infection with Burkholderia cepacia complex (BCC) in patients with CF is often associated with a more rapid decline in lung function. Because of the resistance of BCC to many antibiotics, treatment options are often limited. New therapies to improve outcomes for patients infected with BCC are needed.

However, because of the unpredictable nature of this pulmonary infection in CF, patients with BCC infection have been excluded from many CF therapeutic trials.

Recent published trials in the United States, Australia, and the United Kingdom have all demonstrated clinical benefits from prolonged administration of azithromycin in CF. In these trials, the vast majority of patients were chronically infected with Pseudomonas aeruginosa.

Patients with BCC were excluded from the US and UK trials, and only four patients with BCC infection were enrolled in the Australian trial. Thus, the effectiveness of azithromycin in CF patients infected with BCC is largely unknown and deserves further study.

The two main ways by which azithromycin is thought to help with the chronic lung infections seen in CF are by [a] reducing inflammation and [b] direct effects on the bacteria, in particular P. aeruginosa. BCC pulmonary infection in CF is often associated with a large inflammatory response similar to or more severe than P. aeruginosa infection. If azithromycin works mainly by an anti-inflammatory mechanism, it should also be helpful in CF patients infected with BCC.

Alternatively, azithromycin could have a direct effect on BCC as seen with P. aeruginosa as the two bacteria have many similarities.

Studienübersicht

Status

Unbekannt

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

STUDY DESIGN

  • Overview
  • This is a single center, randomized, double-blinded, placebo-controlled 24 week trial of azithromycin in adults with CF chronically infected with BCC. The investigational therapy will be added to usual therapy in patients who are clinically stable at the time of enrollment. After 168 days, the study drug will be discontinued and participants will be evaluated at 196 days off of study drug for 28 days. At that visit, participants will be invited to continue in an open label observational study of azithromycin for 168 additional days. Thus, the duration of the study will be 52 weeks (364 days).
  • Day 0- Day 168 on Study Drug (24 weeks)
  • Day 169- Day 196 off Study Drug (4 weeks)
  • Day 197 - Day 364 on OPEN label Azithromycin (24 weeks)
  • Measuring primary and secondary endpoints
  • Primary efficacy endpoint
  • Primary efficacy endpoint will be the quantitative changes in lung function as measured by FEV1 in % predicted from baseline to completion of the 24 week treatment period. (refer to Appendix C for ATS guidelines).
  • Primary safety endpoints

  • Primary safety endpoints collected over the 24 week treatment period will be:

    • Adverse events such as gastrointestinal complaints, ototoxicity, tinnitus, hepatitis or leukopenia as determined by:

      (i) open ended questioning of study subjects at study visits (ii) laboratory tests for elevated liver function tests or hematologic abnormalities,

    • Changes in lung microbiology as determined by:[86] (i) Emergent B. cenocepacia (genomovar III) (ii) Emergent non-B. cenocepacia genomovars (iii) Emergent NTM[87] (iv) Emergent azithromycin resistant NTM (v) Emergent Aspergillus species (vi) Emergent MDRO - (S. maltophilia, A. xylosoxidans, or methicillin-resistant S. aureus) (vii) Emergent P. aeruginosa (viii) Emergent azithromycin resistant S. aureus
  • Secondary efficacy endpoints
  • Secondary efficacy endpoints will be:
  • Quantitative changes in lung function as measured by change in relative percent change in FEV1 and FVC from baseline to completion of the 24 week treatment period.
  • Quantitative change in FEV1 and FVC in liters in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo. FEV1 and FVC in liters will be measured according to ATS criteria
  • The number of days until first administration of intravenous antibiotics and/or the use of oral tetracycline derivatives minocycline / doxycycline for seven or more days during the 24 week period.
  • The number of pulmonary exacerbations as defined by need for treatment with intravenous or oral tetracycline derivative antibiotics for an increase in pulmonary symptoms during the 24 week period.
  • The proportion of patients requiring intravenous antibiotics during the 24 week period.
  • The number of days of treatment with intravenous antibiotics given during the 24 week period.
  • The proportion of patients hospitalized.
  • The number of hospital days as calculated by calendar days during the 24 week period.
  • The proportion of patients requiring oral antibiotics during the 24 week period.
  • The number of days of treatment with oral non-tetracycline derivative antibiotics given during the 24 week period.
  • Changes in body weight from baseline to completion of the 24 week treatment period.
  • Change in level of inflammation as measured by the change in serum CRP and ESR from baseline to the end of the 24 week treatment period.

Studientyp

Interventionell

Einschreibung (Voraussichtlich)

45

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Kanada
    • Ontario
      • Toronto, Ontario, Kanada, M5B1W8
        • St. Michael's Hospital

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

19 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Informed consent and verbal assent as appropriate has been provided by the subject
  • Ability to comply with medication use, study visits and study procedures as judged by the site Investigator
  • Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
  • > 18 years of age
  • Body weight > 40 kg
  • BCC present in a sputum/throat culture > 1 year prior to screening and at screening
  • FEV1 % predicted > 30% as calculated by the Knudsen reference equations
  • Room air oximetry > 88% at rest
  • Post-menarche females must be surgically sterile or using an effective form of contraception
  • Predicted to live > 1 year and clinically stable at that time of enrollment as judged by the investigator.

Exclusion Criteria:

  • History of chronic macrolide use, defined as regular macrolide antibiotic use within a three month period prior to enrollment in the study.
  • AST or ALT > 2.5 times the upper limit of normal performed at the local laboratories on two occasions prior to randomization.
  • Investigational drug use within 30 days of screening
  • History of alcohol, illicit drug or medication abuse within 1 year of screening
  • Use of intravenous antibiotics or oral antibiotics within 14 days of screening.
  • Use of low dose oral antibiotics (e.g. macrolides, tetracycline, sulfa) for acne or other conditions within 30 days of screening
  • Use of systemic corticosteroids (> 20 mg of prednisone per day) within 30 days of screening
  • Initiation of TOBI®, high dose ibuprofen, or rhDNase within 60 days of screening
  • History of lung transplantation or currently on lung transplant list
  • History of allergy to a macrolide antibiotic
  • AFB smear positive at screening suggesting current NTM infection.
  • Positive serum pregnancy test at screening (to be performed on all post-menarche females)
  • Absolute neutrophil count < 1000 performed at the local laboratories on two occasions prior to randomization
  • Creatinine > 1.5 times normal performed at the local laboratories on two occasions prior to randomization.
  • Chest x-ray changes or physical findings at screening that would compromise the safety of the patient or the quality of the study data
  • Other major organ dysfunction

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: Azithromycin
participants taking 500 mg tablets orally thrice weekly for 24 weeks
Arzneimittel: Azithromycin
500 mg tablets orally thrice weekly for 24 weeks
Placebo-Komparator: Placebo
Participants taking 500 mg tablets orally thrice weekly for 24 weeks
Arzneimittel: Placebo
tablet orally thrice weekly for 24 weeks

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Zeitfenster
Change in FEV1 in % predicted in CF study subjects treated with azithromycin compared with those CF study subjects treated with placebo.
Zeitfenster: 24 weeks
24 weeks

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Unity Health Toronto

Mitarbeiter

Pfizer
Cystic Fibrosis Foundation

Ermittler

  • Hauptermittler: Elizabeth Tullis, MD, University of Toronto

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. Februar 2006

Primärer Abschluss (Voraussichtlich)

1. Februar 2009

Studienabschluss (Voraussichtlich)

1. Oktober 2009

Studienanmeldedaten

Zuerst eingereicht

2. März 2006

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

2. März 2006

Zuerst gepostet (Schätzen)

3. März 2006

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

31. Juli 2009

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

30. Juli 2009

Zuletzt verifiziert

1. Juli 2009

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • AZ 0003
  • TULLIS04A0

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