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AspergillosisPhase 2/3NCT00263315

Inhalation of Liposomal Amphotericin B to Prevent Invasive Aspergillosis

A Phase 2/3 study testing nebulised liposomal amphotericin B in people with Aspergillosis, run by Erasmus Medical Center at 2 sites in Netherlands.

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

A Phase II/III randomized double-blind study comparing the safety and the efficacy of a weekly administration of 25 mg nebulized AmBisome with nebulized placebo solution to prevent invasive pulmonary aspergillosis in neutropenic hemato-oncologic patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Aspergillosis
What is being tested?
nebulised liposomal amphotericin B
How many people
320 participants
Where
2 sitesNetherlands
Study dates
Jan 2000to May 2006
Phase
Phase 2/3
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female hospitalized patients aged > 18 yr
  • The patient has a hematologic malignancy or will receive a bone-marrow transplant
  • The patient starts with a course of chemotherapy within 4 days or is already neutropenic at admission
  • The expected duration of severe neutropenia (PMN<0.5x10*9/L) following study entry is > 10 days
  • The patient is receiving oral antibiotic prophylaxis and fluconazole
  • Written informed consent has been obtained

Who cannot join

  • The patient shows evidence of a pulmonary fungal infection or a fungal sinusitis at trial entry
  • The concomitant use of systemic anti-aspergillus treatment such as itraconazole or any intravenous formulation of amphotericin B at study entry
  • Known hypersensitivity to amphotericin B
  • Any evidence of pneumonia or pneumonitis at trial entry
  • Any impossibility to use a nebulizer properly
  • Expected survival < 3 months at entry
  • Pregnancy

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • Erasmus MC centrumlocatie

    Rotterdam

  • Erasmus MC locatie Daniel den Hoed

    Rotterdam

Other trials in Netherlands

About this study

Official title: Nebulized Liposomal Amphotericin B (Ambisome) Versus Nebulized Placebo for the Prophylaxis of Invasive Pulmonary Aspergillosis in Haematological Patients With Prolonged Neutropenia. A Randomized Clinical Trial.

A Phase II/III randomized double-blind study comparing the safety and the efficacy of a weekly administration of 25 mg nebulized AmBisome with nebulized placebo solution to prevent invasive pulmonary aspergillosis in neutropenic hemato-oncologic patients.

Read the detailed description

The morbidity, mortality and costs of invasive pulmonary aspergillosis (IPA) in neutropenic patients are high. An effective intervention to prevent IPA would therefore be welcome. The incidence of IPA in neutropenic hematology patients in our institution was recently estimated to be 5-10%. Currently, only HEPA filtration is routinely used for the prevention of IPA. In 1988, Schmitt et al. showed a significant delayed mortality in rat model of IPA when rats were treated with aerosolized conventional amphotericin-B (amB) two days before infection (1). Conventional amB may interfere with surfactant function in the lungs. In contrast, liposomal amphotericin-B contains phospholipids that are structurally related to surfactant and inhibits natural surfactant function only slightly. Furthermore, in rats, mean concentrations of AmB in lungs were 3.7 times higher at day one and almost 6 times higher at day seven after a single dose treatment with aerosolized liposomal amB when compared with conventional AmB (2). Only one non-placebo controlled randomized clinical trial evaluated the prophylactic use of inhalation therapy with conventional amB for the prevention of IPA and a non-significant 43% reduction was observed (3). We postulate that the weekly inhalation of liposomal AmB in neutropenic hematology patients can prevent IPA.

In this randomised placebo controlled clinical trial we compare the safety and efficacy of the administration of nebulized liposomal AmB (2x/week) with placebo for the prevention of IPA in haematological patients with an expected duration of neutropenia of >10d. To demonstrate a reduction in incidence of invasive pulmonary aspergillosis from 7% to 1%, a total of 170 neutropenic episodes in each arm will be included (power 80%, two-tailed alfa=0.05). The primary efficacy endpoint is the cumulative percentage of patients developing a proven or probable IPA. Per protocol serum galactomannan levels are monitored 2x/week and a HR-CT of the lungs will be performed for unexplained fever (>5d) unresponsive to broad-spectrum antibiotic therapy. EORTC/MSG criteria are used for diagnosis of IPA. The primary safety endpoint is a premature discontinuation of the study drug for >1week due to intolerance.

Conditions
Aspergillosis
Being tested
nebulised liposomal amphotericin B
Keywords
aspergillosis, mycosis, neutropenia, primary prevention, hematologic diseases, amphotericin B, AmBisome, liposomal amphotericin B
Medical subject headings
Aspergillosis, Mycoses, Neutropenia, Hematologic Diseases

What participants receive

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

  • nebulised liposomal amphotericin BDrug

What is being measured

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

  1. SAFETY: Discontinuation for >1week due to intolerance

  2. EFFICACY: Proven/probable invasive pulmonary aspergillosis

Secondary outcomes (11)

  1. SAFETY STUDY:

  2. A probably or definitely related AE of the respiratory tract (CTC grade > 2)

  3. Any probably or definitely related AE by type and severity (CTC grade > 2)

  4. Requirement of pre-medication to tolerate nebulization of the study drug

  5. Spirometric changes after inhalation

  6. EFFICACY STUDY:

  7. Proven, probable or possible invasive pulmonary aspergillosis

  8. A confirmed positive serum galactomannan concentration of 0.5 ng/ml or more

  9. The use of systemic antifungal drugs (days) during the neutropenic episodes

  10. The number of days of fever of unknown origin during neutropenia

  11. Mortality due to a pulmonary fungal infection

Timeline

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

  1. First posted8 Dec 2005 (estimated)
  2. Study startJan 2000
  3. Study completionMay 2006

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 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
320 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00263315
Sponsor's protocol ID
METC 191.137/2000/088
Status last verified
Aug 2006
First submitted
7 Dec 2005
Last updated
18 Aug 2006
Results posted
No

Publications

  • Schmitt HJ, Bernard EM, Andrade J, Edwards F, Schmitt B, Armstrong D. MIC and fungicidal activity of terbinafine against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother. 1988 May;32(5):780-1. doi: 10.1128/AAC.32.5.780.

    PubMed 3134851

  • Cicogna CE, White MH, Bernard EM, Ishimura T, Sun M, Tong WP, Armstrong D. Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1997 Feb;41(2):259-61. doi: 10.1128/AAC.41.2.259.

    PubMed 9021176

  • Schwartz S, Behre G, Heinemann V, Wandt H, Schilling E, Arning M, Trittin A, Kern WV, Boenisch O, Bosse D, Lenz K, Ludwig WD, Hiddemann W, Siegert W, Beyer J. Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood. 1999 Jun 1;93(11):3654-61.

    PubMed 10339471

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing nebulised liposomal amphotericin B in people with Aspergillosis, run by Erasmus Medical Center at 2 sites in Netherlands.

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 6 inclusion and 7 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 18 Aug 2006. 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 Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

SAFETY: Discontinuation for >1week due to intolerance. The study lists 2 primary outcomes in all. 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 NCT00263315, which also lists 3 linked publications.

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 18 Aug 2006.

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