Invader Fungal InfectionPhase 4NCT00386802

Antifungal Use in Oncohematological Neutropenic Patients

A Phase 4 study testing Antifungal drug. VORICONAZOL. (VFEND®) in people with Invader Fungal Infection, run by PETHEMA Foundation at 13 sites in Spain.

Completed

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

Official record

Search all trials

Trial summary

Primary purpose: Frequency of use of broad-spectrum antifungals in the episode of neutropenia. Secondary purposes:To determine the safety and toxicity measure by: 1. Frequency of Invader Fungal Infection. 2. Read more about this study

Who is it for?: Ages 2 years and older
Conditions the study is for: Invader Fungal Infection
What is being tested?: Antifungal drug. VORICONAZOL. (VFEND®)
Type of treatment: Pill or oral medicine, Injection or infusion
How many people: 115 participants
Where: 13 sitesSpain
Study dates: Aug 2006to Jan 2009
Phase: Phase 4
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 2 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Adult and pediatric patients (from 2 years old on) with diagnostic of hematologic malignancies or solid tumour.
Patients who will develop neutropenia (<500PN) post chemotherapy or post Bone Marrow Transplantation (BMT) that according to the center, they can receive empirical antifungal treatment of broad-spectrum.
Controlled patients with galactomannan in blood twice weekly.
Empirical antibacterial therapy of broad-spectrum, as possible the Pethema protocol that it is activated in this moment. Also it will be validated the monotherapy with carbapenemic or cephalosporin of fourth or third generation, or the biotherapy.
Inclusion of patient since the start of his chemotherapy or therapy of preparation.
If a bacterial infection is documented, it will be treated and controlled before to begin the empirical antifungal treatment.

Show all 15Show fewer

Signed of informed consent.
Negative pregnancy test in fertile patients
The patients will be excluded if they have settled by Aspergillus, C.krusei or C.gladiata in this episode of neutropenia, or in other and if they lack of the results of the cultures of vigilance in the present episode. If it presents positive result for any of those pathogens the empirical treatment will must be with a antifungal that it covers good (amphotericin, caspofungin or voriconazole) and not with fluconazole, then those patients will not follow this protocol.
To receive drugs, which aren´t indicated in patients in treatment with voriconazole and/or with fluconazole.
The patients will not be excluded if they receive antibacterial prophylaxis oral with quinolones, macrolides, etc., or stimulating factors G-CSF, GM-CSF or similar.
Cause of exclusion will be the fault of fulfilment of inclusion criteria. Above all the patients will be excluded if they:
have fault of twice weekly monitoring with galactomannan.
have a bacterial infection not very good treated and controlled before to can begin the empirical antifungal infection (according to definition previous)
have at final, a neutropenia of short stay that it has a risk important of Invader Fungal Infection. This data naturally will not know in the moment of include at patient in the study. It defines as neutropenia of short stay if it last out less of 5 days.

Who cannot join

Use of antifungal prophylaxis with triazoles with activity against Aspergillus, or use of others systematics antifungal by previous Invader Fungal Infection or other reasons.
Use prophylactic of fluconazole to dose higher than 100 mg/day.
Allergy to azoles
To have a invader fungal infection at start of episode of neutropenia with fever.
High effect in the unity of insulation of Candida strong to fluconazole that to opinion of center it hasn´t appropriate to include in a protocol where it is considered the use of empirical fluconazole.
Neutropenias made by aplastic anemia or other faults of bone similar.

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

Spain13 sites

Hospital Clínic
Barcelona, Barcelona
Hospital Virgen de las Nieves
Granada, Granada
Hospital General de Jerez de la Frontera
Jerez de la Frontera, Cádiz
Hospital General Universitario Gregorio Marañón, Madrid
Madrid, Madrid
Hospital Universitario de la Princesa
Madrid, Madrid
Hospital Universitario Ramón y Cajal, Madrid
Madrid, Madrid
Hospital Universitario Morales Meseguer, Murcia
Murcia, Murcia
Hospital Son Llatzer
Palma de Mallorca, Mallorca
Hospital Clínico Universitario de Salamanca
Salamanca
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria
Hospital Clínico Universitario de Valencia
Valencia, Valencia
Hospital Universitario La Fe
Valencia, Valencia
Hospital Clínico Lozano Blesa
Zaragoza, Zaragoza

Other trials in Spain

About this study

Official title: ANTIVORIFUNGOL:Strategy of Antifungal Use in Oncohematological Neutropenic Patients. Use of Voriconazole as Early Treatment.

Primary purpose: Frequency of use of broad-spectrum antifungals in the episode of neutropenia.

Secondary purposes:To determine the safety and toxicity measure by:

Frequency of Invader Fungal Infection.
Frequency of global use of broad-spectrum antifungals as amphotericine, itraconazole, voriconazole, caspofungin, terbinafine, during the period of study.
Mortality
Development of nephrotoxicity
Use of galactomannan in this clinical context
Time of administration of empirical antifungal therapy of broad-spectrum.

Read the detailed description

Clinical trial with a pharmaceutical speciality in the conditions of authorized use

Conditions: Invader Fungal Infection
Being tested: Antifungal drug. VORICONAZOL. (VFEND®)
Keywords: Neutropenia, Antifungals
Medical subject headings: Neutropenia

What participants receive

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

Antifungal drug. VORICONAZOL. (VFEND®)Drug
I.V charge dose 6 mg/kg/12h (2 doses) Maintenance iv treatment 4 mg/kg/12h during 6 days, followed by oral treatment (200 mg/12h)

What is being measured

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

Frequency of use of broad-spectrum antifungals in the episode of neutropenia.
Measured: 2 years

Secondary outcomes (7)

To determine the safety and toxicity measure by:
Measured: 1 year
Frequency of Invader Fungal Infection.
Measured: 2 years
Frequency of global use of broad-spectrum antifungals as amphotericine, itraconazole, voriconazole, caspofungin, terbinafine, during the period of study.
Measured: 2 years
Mortality
Measured: 2 years
Development of nephrotoxicity
Measured: 2 years
Use of galactomannan in this clinical context
Measured: 2 years
Time of administration of empirical antifungal therapy of broad-spectrum.
Measured: 6 months

Timeline

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

Aug 2006Jan 2009

First posted12 Oct 2006 (estimated)
Study startAug 2006
Primary completionDec 2008
Study completionJan 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (37)Papers the sponsor has linked to this study.
Other trials for Invader Fungal InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 115 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00386802
Sponsor's protocol ID: 2005-004973-55
Other IDs: ANTIVORIFUNGOL, 2005
Status last verified: Sep 2009
First submitted: 11 Oct 2006
Last updated: 18 Sep 2009
Results posted: No
Data monitoring committee: Yes

Publications

Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Br J Haematol. 2002 Apr;117(1):40-6. doi: 10.1046/j.1365-2141.2002.03414.x.
PubMed 11918531
Young RC, Bennett JE, Vogel CL, Carbone PP, DeVita VT. Aspergillosis. The spectrum of the disease in 98 patients. Medicine (Baltimore). 1970 Mar;49(2):147-73. doi: 10.1097/00005792-197003000-00002. No abstract available.
PubMed 4913991
Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect. 1996 Jul;33(1):23-32. doi: 10.1016/s0163-4453(96)92700-0.
PubMed 8842991
Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. doi: 10.1016/0002-9343(82)90594-0. No abstract available.
PubMed 7058815
Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group. Am J Med. 1989 Jun;86(6 Pt 1):668-72. doi: 10.1016/0002-9343(89)90441-5.
PubMed 2658574
Wingard JR, Kubilis P, Lee L, Yee G, White M, Walshe L, Bowden R, Anaissie E, Hiemenz J, Lister J. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis. 1999 Dec;29(6):1402-7. doi: 10.1086/313498.
PubMed 10585786
Bates DW, Su L, Yu DT, Chertow GM, Seger DL, Gomes DR, Dasbach EJ, Platt R. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis. 2001 Mar 1;32(5):686-93. doi: 10.1086/319211. Epub 2001 Feb 21.
PubMed 11229835
Harbarth S, Burke JP, Lloyd JF, Evans RS, Pestotnik SL, Samore MH. Clinical and economic outcomes of conventional amphotericin B-associated nephrotoxicity. Clin Infect Dis. 2002 Dec 15;35(12):e120-7. doi: 10.1086/344468. Epub 2002 Dec 2.
PubMed 12471588
Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004 Sep 30;351(14):1391-402. doi: 10.1056/NEJMoa040446.
PubMed 15459300
Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. doi: 10.1056/NEJM200201243460403.
PubMed 11807146
Malik IA, Moid I, Aziz Z, Khan S, Suleman M. A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med. 1998 Dec;105(6):478-83. doi: 10.1016/s0002-9343(98)00326-x.
PubMed 9870832
Viscoli C, Castagnola E, Van Lint MT, Moroni C, Garaventa A, Rossi MR, Fanci R, Menichetti F, Caselli D, Giacchino M, Congiu M. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer. 1996 May;32A(5):814-20. doi: 10.1016/0959-8049(95)00619-2.
PubMed 9081359
Winston DJ, Hathorn JW, Schuster MG, Schiller GJ, Territo MC. A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med. 2000 Mar;108(4):282-9. doi: 10.1016/s0002-9343(99)00457-x.
PubMed 11014720
McLintock LA, Jordanides NE, Allan EK, Copland M, Stewart K, Parker A, Devaney M, Holyoake TL, Jones BL. The use of a risk group stratification in the management of invasive fungal infection: a prospective validation. Br J Haematol. 2004 Feb;124(3):403-4. doi: 10.1046/j.1365-2141.2003.04794.x. No abstract available.
PubMed 14717790
Wheat LJ. Rapid diagnosis of invasive aspergillosis by antigen detection. Transpl Infect Dis. 2003 Dec;5(4):158-66. doi: 10.1111/j.1399-3062.2003.00031.x.
PubMed 14987199

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: ANTIVORIFUNGOL:Strategy of Antifungal Use in Oncohematological Neutropenic Patients. Use of Voriconazole as Early Treatment.
ClinicalTrials.gov ID: NCT00386802
Acronym / sponsor ID: 2005-004973-55
Conditions: Invader Fungal Infection
Keywords: Neutropenia, Antifungals
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 115 participants (estimated)
Lead sponsor: PETHEMA FoundationUniversity, hospital or other
Study start: Aug 2006
Primary completion: Dec 2008 (actual)
Study completion: Jan 2009 (actual)
First posted: 12 Oct 2006 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary purpose: Frequency of use of broad-spectrum antifungals in the episode of neutropenia.

Secondary purposes:To determine the safety and toxicity measure by:

Frequency of Invader Fungal Infection.
Frequency of global use of broad-spectrum antifungals as amphotericine, itraconazole, voriconazole, caspofungin, terbinafine, during the period of study.
Mortality
Development of nephrotoxicity
Use of galactomannan in this clinical context
Time of administration of empirical antifungal therapy of broad-spectrum.

Detailed description

Clinical trial with a pharmaceutical speciality in the conditions of authorized use

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 2 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (15 listed)

Adult and pediatric patients (from 2 years old on) with diagnostic of hematologic malignancies or solid tumour.
Patients who will develop neutropenia (<500PN) post chemotherapy or post Bone Marrow Transplantation (BMT) that according to the center, they can receive empirical antifungal treatment of broad-spectrum.
Controlled patients with galactomannan in blood twice weekly.
Empirical antibacterial therapy of broad-spectrum, as possible the Pethema protocol that it is activated in this moment. Also it will be validated the monotherapy with carbapenemic or cephalosporin of fourth or third generation, or the biotherapy.
Inclusion of patient since the start of his chemotherapy or therapy of preparation.

Key exclusion criteria (6 listed)

Use of antifungal prophylaxis with triazoles with activity against Aspergillus, or use of others systematics antifungal by previous Invader Fungal Infection or other reasons.
Use prophylactic of fluconazole to dose higher than 100 mg/day.
Allergy to azoles
To have a invader fungal infection at start of episode of neutropenia with fever.
High effect in the unity of insulation of Candida strong to fluconazole that to opinion of center it hasn´t appropriate to include in a protocol where it is considered the use of empirical fluconazole.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Antifungal drug. VORICONAZOL. (VFEND®)I.V charge dose 6 mg/kg/12h (2 doses) Maintenance iv treatment 4 mg/kg/12h during 6 days, followed by oral treatment (200 mg/12h)	Drug	–

Primary outcome

Frequency of use of broad-spectrum antifungals in the episode of neutropenia.
Time frame: 2 years

7 secondary outcomes

To determine the safety and toxicity measure by:
Time frame: 1 year
Frequency of Invader Fungal Infection.
Time frame: 2 years
Frequency of global use of broad-spectrum antifungals as amphotericine, itraconazole, voriconazole, caspofungin, terbinafine, during the period of study.
Time frame: 2 years
Mortality
Time frame: 2 years
Development of nephrotoxicity
Time frame: 2 years
Use of galactomannan in this clinical context
Time frame: 2 years
Time of administration of empirical antifungal therapy of broad-spectrum.
Time frame: 6 months

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2009.
Background: PubMed 11918531Kami M, Machida U, Okuzumi K, Matsumura T, Mori Si S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Br J Haematol. 2002 Apr;117(1):40-6. doi: 10.1046/j.1365-2141.2002.03414.x.
Background: PubMed 4913991Young RC, Bennett JE, Vogel CL, Carbone PP, DeVita VT. Aspergillosis. The spectrum of the disease in 98 patients. Medicine (Baltimore). 1970 Mar;49(2):147-73. doi: 10.1097/00005792-197003000-00002. No abstract available.
Background: PubMed 8842991Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect. 1996 Jul;33(1):23-32. doi: 10.1016/s0163-4453(96)92700-0.
Background: PubMed 7058815Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. doi: 10.1016/0002-9343(82)90594-0. No abstract available.
Background: PubMed 2658574Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group. Am J Med. 1989 Jun;86(6 Pt 1):668-72. doi: 10.1016/0002-9343(89)90441-5.
Background: PubMed 10585786Wingard JR, Kubilis P, Lee L, Yee G, White M, Walshe L, Bowden R, Anaissie E, Hiemenz J, Lister J. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis. 1999 Dec;29(6):1402-7. doi: 10.1086/313498.
Background: PubMed 11229835Bates DW, Su L, Yu DT, Chertow GM, Seger DL, Gomes DR, Dasbach EJ, Platt R. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis. 2001 Mar 1;32(5):686-93. doi: 10.1086/319211. Epub 2001 Feb 21.
Background: PubMed 12471588Harbarth S, Burke JP, Lloyd JF, Evans RS, Pestotnik SL, Samore MH. Clinical and economic outcomes of conventional amphotericin B-associated nephrotoxicity. Clin Infect Dis. 2002 Dec 15;35(12):e120-7. doi: 10.1086/344468. Epub 2002 Dec 2.
Background: PubMed 15459300Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004 Sep 30;351(14):1391-402. doi: 10.1056/NEJMoa040446.
Background: PubMed 11807146Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. doi: 10.1056/NEJM200201243460403.
Background: PubMed 9870832Malik IA, Moid I, Aziz Z, Khan S, Suleman M. A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med. 1998 Dec;105(6):478-83. doi: 10.1016/s0002-9343(98)00326-x.
Background: PubMed 9081359Viscoli C, Castagnola E, Van Lint MT, Moroni C, Garaventa A, Rossi MR, Fanci R, Menichetti F, Caselli D, Giacchino M, Congiu M. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer. 1996 May;32A(5):814-20. doi: 10.1016/0959-8049(95)00619-2.
Spanish association of HaematologyLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

de la Cámara Rafael, Dr principal investigator

Hospital Universitario de la Princesa, Madrid

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Antifungal drug. VORICONAZOL. (VFEND®) in people with Invader Fungal Infection, run by PETHEMA Foundation at 13 sites in Spain.

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 15 inclusion and 6 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 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain. 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 phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Frequency of use of broad-spectrum antifungals in the episode of neutropenia. (time frame: 2 years). 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 NCT00386802, which also lists 37 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 Sep 2009.