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Trial record 1 of 1 for:    NCT00143312
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Voriconazole for Secondary Prophylaxis of Invasive Fungal Infections in Patients With Allogeneic Stem Cell Transplants (VOSIFI)

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ClinicalTrials.gov Identifier: NCT00143312
Recruitment Status : Completed
First Posted : September 2, 2005
Results First Posted : June 1, 2009
Last Update Posted : October 6, 2009
Sponsor:
Collaborator:
European Group for Blood and Marrow Transplantation
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Prophylaxis Of Invasive Fungal Infections
Intervention Drug: voriconazole
Enrollment 45
Recruitment Details  
Pre-assignment Details Subjects with proven or probable Invasive Fungal Infection (IFI) in the previous 12 months, who were receiving an allogeneic Stem Cell Transplant (SCT) for any hematologic disease, were enrolled into the study if all other inclusion/exclusion criteria were met.
Arm/Group Title Voriconazole
Hide Arm/Group Description All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Period Title: Overall Study
Started 45
Completed 29
Not Completed 16
Reason Not Completed
Death             11
Adverse Event             2
Lost to Follow-up             1
Other             1
Withdrawal by Subject             1
Arm/Group Title Voriconazole
Hide Arm/Group Description All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Baseline Participants 45
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants
48.4  (14.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Female
17
  37.8%
Male
28
  62.2%
1.Primary Outcome
Title Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit
Hide Description Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: participants
3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Crude IFI Rate (percent) at 12 months
Estimated Value 7
Confidence Interval 95%
2 to 19
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter IFI Rate (percent) at 12 months
Estimated Value 10
Confidence Interval 95%
2 to 27
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit
Hide Description Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 34
Measure Type: Number
Unit of Measure: participants
3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter IFI Rate (percent) at 6 months
Estimated Value 8.82
Confidence Interval 95%
2 to 24
Estimation Comments Exact 95% Confidence Interval For Proportion; Expressed as a percentage
3.Secondary Outcome
Title Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit
Hide Description Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit
Time Frame 150 days
Hide Outcome Measure Data
Hide Analysis Population Description
Complete case analysis (ie, outcome must be observed and/or subject must be evaluable for entire period of interest) using modified intent-to-treat (MITT) population (ie, subjects had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & previous diagnosis of proven or probable IFI, confirmed by Data Review Committee).
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 34
Measure Type: Number
Unit of Measure: participants
3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter IFI Rate (percent) at End of Prophylaxis
Estimated Value 8.82
Confidence Interval 95%
2 to 24
Estimation Comments Exact 95% Confidence Interval For Proportion; Expressed as a percentage
4.Secondary Outcome
Title Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
Hide Description Time to occurrence of proven or probable IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI since the exact day on which the IFI began will not be known.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Three subjects in the MITT population experienced an IFI.
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: days
time to recurrent IFI (first subject) 6
time to recurrent IFI (second subject) 22
time to recurrent IFI (third subject) 81
5.Secondary Outcome
Title Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI)
Hide Description Time to occurrence of proven or probable new (new pathogen) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. One subject in the MITT population experienced a new IFI.
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: days
81
6.Secondary Outcome
Title Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI)
Hide Description Time to occurrence of proven or probable recurrent (same pathogen as baseline) IFI from the start of voriconazole prophylaxis. Time to occurrence is strictly time to recorded diagnosis of IFI. The pathogen identified as the positive culture recorded nearest to, but not after, the proven or probable IFI, was assumed to be responsible for the IFI.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (MITT) population (considered evaluable for efficacy) consisted of all subjects who had at least 1 dose of voriconazole & at least 1 post-enrollment efficacy assessment & had a previous diagnosis of proven or probable IFI, confirmed by the Data Review Committee. Two subjects experienced a recurrent proven or probable IFI.
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: days
time to IFI (first subject) 6
time to IFI (second subject) 22
7.Secondary Outcome
Title Survival Without Proven or Probable Invasive Fungal Infection (IFI)
Hide Description Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits
Time Frame 6 months, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Complete case analysis using MITT population (ie, all subjects who had at least 1 dose of study medication & at least 1 post-enrollment efficacy assessment & a previous diagnosis of proven or probable IFI, confirmed by Data Review Committee) & either provided an IFI assessment at follow-up visit, died or experienced an IFI before that visit.
Arm/Group Title Voriconazole
Hide Arm/Group Description:
All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
Overall Number of Participants Analyzed 39
Measure Type: Number
Unit of Measure: participants
survived free of IFI until 6 months 31
survived free of IFI until 12 months 27
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter survive free of IFI (percent): 6 months
Estimated Value 79
Confidence Interval 95%
64 to 91
Estimation Comments Exact 95% Confidence Interval For Proportion; Expressed as a percentage
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Voriconazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter survive free of IFI (percent): 12 months
Estimated Value 69
Confidence Interval 95%
52 to 83
Estimation Comments Exact 95% Confidence Interval For Proportion; Expressed as a percentage
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Voriconazole
Hide Arm/Group Description All subjects received voriconazole as study medication for prophylaxis, for a minimum of 100 days after transplant. Subjects received an intravenous (IV; 6 mg/kg)) or oral (PO; 400 mg) loading dose every 12 hours (q12h) for 2 doses, followed by maintenance (i.e., prophylactic) doses of 4 mg/kg IV q12h or 200 mg PO q12h, if the subject weighed ≥40 kg. If the subject weighed <40 kg, the PO loading dose was 200 mg PO q12h for 2 doses, followed by maintenance doses of 100 mg PO q12h.
All-Cause Mortality
Voriconazole
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Voriconazole
Affected / at Risk (%)
Total   23/45 (51.11%) 
Blood and lymphatic system disorders   
Haemolysis  1  1/45 (2.22%) 
Pancytopenia   1/45 (2.22%) 
Thrombocytopenia   1/45 (2.22%) 
Cardiac disorders   
Atrial fibrillation   1/45 (2.22%) 
Palpitations   1/45 (2.22%) 
Tachycardia   1/45 (2.22%) 
Eye disorders   
Eye swelling   1/45 (2.22%) 
Gastrointestinal disorders   
Abdominal pain   1/45 (2.22%) 
Diarrhoea   2/45 (4.44%) 
Nausea   1/45 (2.22%) 
Vomiting   3/45 (6.67%) 
General disorders   
Disease progression   1/45 (2.22%) 
Pyrexia   2/45 (4.44%) 
Hepatobiliary disorders   
Cholecystitis   1/45 (2.22%) 
Cholestasis   1/45 (2.22%) 
Hepatitis toxic   1/45 (2.22%) 
Hepatomegaly   1/45 (2.22%) 
Hepatotoxicity   2/45 (4.44%) 
Hyperbilirubinaemia   1/45 (2.22%) 
Immune system disorders   
Graft versus host disease   2/45 (4.44%) 
Infections and infestations   
Cytomegalovirus infection   1/45 (2.22%) 
Diarrhoea infectious   1/45 (2.22%) 
Encephalitis herpes   1/45 (2.22%) 
Pneumonia   1/45 (2.22%) 
Sepsis   2/45 (4.44%) 
Investigations   
Blood creatine increased   1/45 (2.22%) 
Electrocardiogram change   1/45 (2.22%) 
Liver function test abnormal   1/45 (2.22%) 
Sputum culture positive   1/45 (2.22%) 
Weight increased   1/45 (2.22%) 
Metabolism and nutrition disorders   
Hyperglycaemia   1/45 (2.22%) 
Musculoskeletal and connective tissue disorders   
Myalgia   1/45 (2.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute myeloid leukaemia recurrent   1/45 (2.22%) 
Central nervous system leukaemia   1/45 (2.22%) 
Nervous system disorders   
Facial paresis   1/45 (2.22%) 
Headache   1/45 (2.22%) 
Loss of consciousness   1/45 (2.22%) 
Psychiatric disorders   
Hallucination   1/45 (2.22%) 
Renal and urinary disorders   
Renal failure   1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders   
Productive cough   1/45 (2.22%) 
Pulmonary oedema   1/45 (2.22%) 
Skin and subcutaneous tissue disorders   
Erythema   1/45 (2.22%) 
Vascular disorders   
Hypertension   1/45 (2.22%) 
Hypotension   1/45 (2.22%) 
Venoocclusive disease   1/45 (2.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v11.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Voriconazole
Affected / at Risk (%)
Total   42/45 (93.33%) 
Blood and lymphatic system disorders   
Anaemia  1  7/45 (15.56%) 
Febrile neutropenia  1  8/45 (17.78%) 
Neutropenia  2  3/45 (6.67%) 
Thrombocytopenia  1  7/45 (15.56%) 
Eye disorders   
Conjunctivitis  2  3/45 (6.67%) 
Gastrointestinal disorders   
Abdominal pain  1  7/45 (15.56%) 
Abdominal pain upper  1  6/45 (13.33%) 
Constipation  2  5/45 (11.11%) 
Diarrhoea  1  15/45 (33.33%) 
Dyspepsia  2  3/45 (6.67%) 
Nausea  2  5/45 (11.11%) 
Vomiting  1  13/45 (28.89%) 
General disorders   
Asthenia  2  4/45 (8.89%) 
Chills  2  5/45 (11.11%) 
Fatigue  2  4/45 (8.89%) 
Mucosal inflammation  1  17/45 (37.78%) 
Oedema peripheral  2  5/45 (11.11%) 
Pyrexia  1  13/45 (28.89%) 
Hepatobiliary disorders   
Cholestasis  2  3/45 (6.67%) 
Hepatotoxicity  2  3/45 (6.67%) 
Immune system disorders   
Acute graft versus host disease  2  3/45 (6.67%) 
Chronic graft versus host disease  2  3/45 (6.67%) 
Graft versus host disease  1  12/45 (26.67%) 
Infections and infestations   
Cytomegalovirus infection  2  4/45 (8.89%) 
Sinusitis  2  3/45 (6.67%) 
Injury, poisoning and procedural complications   
Transfusion reaction  2  3/45 (6.67%) 
Investigations   
Liver function test abnormal  2  4/45 (8.89%) 
Weight decreased  2  3/45 (6.67%) 
Metabolism and nutrition disorders   
Anorexia  2  4/45 (8.89%) 
Hypokalaemia  2  3/45 (6.67%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal pain  2  3/45 (6.67%) 
Pain in extremity  2  3/45 (6.67%) 
Nervous system disorders   
Headache  1  13/45 (28.89%) 
Psychiatric disorders   
Anxiety  2  3/45 (6.67%) 
Hallucination  2  3/45 (6.67%) 
Insomnia  1  7/45 (15.56%) 
Sleep disorder  2  3/45 (6.67%) 
Respiratory, thoracic and mediastinal disorders   
Cough  2  3/45 (6.67%) 
Skin and subcutaneous tissue disorders   
Erythema  2  5/45 (11.11%) 
Rash  1  6/45 (13.33%) 
Vascular disorders   
Hypertension  1  8/45 (17.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v11.0
2
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.govCallCenter@pfizer.com
Layout table for additonal information
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00143312    
Other Study ID Numbers: A1501038
First Submitted: August 31, 2005
First Posted: September 2, 2005
Results First Submitted: April 2, 2009
Results First Posted: June 1, 2009
Last Update Posted: October 6, 2009