Trial Outcomes & Findings for Voriconazole for Secondary Prophylaxis of Invasive Fungal Infections in Patients With Allogeneic Stem Cell Transplants (NCT NCT00143312)
NCT ID: NCT00143312
Last Updated: 2009-10-06
Results Overview
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up
COMPLETED
PHASE4
45 participants
12 months
2009-10-06
Participant Flow
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.
Participant milestones
| Measure |
Voriconazole
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 Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
29
|
|
Overall Study
NOT COMPLETED
|
16
|
Reasons for withdrawal
| Measure |
Voriconazole
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 Study
Death
|
11
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Other
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Voriconazole for Secondary Prophylaxis of Invasive Fungal Infections in Patients With Allogeneic Stem Cell Transplants
Baseline characteristics by cohort
| Measure |
Voriconazole
n=45 Participants
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.
|
|---|---|
|
Age Continuous
|
48.4 years
STANDARD_DEVIATION 14.1 • n=93 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: 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).
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 12-month follow up
Outcome measures
| Measure |
Voriconazole
n=30 Participants
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.
|
|---|---|
|
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 12-month Follow-up Visit
|
3 participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: 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).
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until 6-month follow up
Outcome measures
| Measure |
Voriconazole
n=34 Participants
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.
|
|---|---|
|
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Prophylaxis Until 6-month Follow-up Visit
|
3 participants
|
SECONDARY outcome
Timeframe: 150 daysPopulation: 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).
Number of participants developing a proven or probable IFI from start of voriconazole prophylaxis until the End of Prophylaxis visit
Outcome measures
| Measure |
Voriconazole
n=34 Participants
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.
|
|---|---|
|
Occurrence of Proven or Probable Invasive Fungal Infection (IFI): Start of Voriconazole Prophylaxis Until End of Prophylaxis Visit
|
3 participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Voriconazole
n=42 Participants
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.
|
|---|---|
|
Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
time to recurrent IFI (first subject)
|
6 days
|
|
Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
time to recurrent IFI (second subject)
|
22 days
|
|
Time to Occurrence of Proven or Probable Invasive Fungal Infection (IFI)
time to recurrent IFI (third subject)
|
81 days
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Voriconazole
n=42 Participants
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.
|
|---|---|
|
Time to Occurrence of Proven or Probable New (New Pathogen) Invasive Fungal Infection (IFI)
|
81 days
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Voriconazole
n=42 Participants
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.
|
|---|---|
|
Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI)
time to IFI (first subject)
|
6 days
|
|
Time to Occurrence of Proven or Probable Recurrent Invasive Fungal Infection (IFI) (Same Pathogen as Previous Baseline IFI)
time to IFI (second subject)
|
22 days
|
SECONDARY outcome
Timeframe: 6 months, 12 monthsPopulation: 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.
Number of participants who survive (ie., are alive) without proven or probable IFI at each of the 6 and 12 month follow-up visits
Outcome measures
| Measure |
Voriconazole
n=39 Participants
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.
|
|---|---|
|
Survival Without Proven or Probable Invasive Fungal Infection (IFI)
survived free of IFI until 6 months
|
31 participants
|
|
Survival Without Proven or Probable Invasive Fungal Infection (IFI)
survived free of IFI until 12 months
|
27 participants
|
Adverse Events
Voriconazole
Serious adverse events
| Measure |
Voriconazole
n=45 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.2%
1/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia recurrent
|
2.2%
1/45
|
|
Cardiac disorders
Atrial fibrillation
|
2.2%
1/45
|
|
Investigations
Blood creatine increased
|
2.2%
1/45
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system leukaemia
|
2.2%
1/45
|
|
Hepatobiliary disorders
Cholecystitis
|
2.2%
1/45
|
|
Hepatobiliary disorders
Cholestasis
|
2.2%
1/45
|
|
Infections and infestations
Cytomegalovirus infection
|
2.2%
1/45
|
|
Gastrointestinal disorders
Diarrhoea
|
4.4%
2/45
|
|
Infections and infestations
Diarrhoea infectious
|
2.2%
1/45
|
|
General disorders
Disease progression
|
2.2%
1/45
|
|
Investigations
Electrocardiogram change
|
2.2%
1/45
|
|
Infections and infestations
Encephalitis herpes
|
2.2%
1/45
|
|
Skin and subcutaneous tissue disorders
Erythema
|
2.2%
1/45
|
|
Eye disorders
Eye swelling
|
2.2%
1/45
|
|
Nervous system disorders
Facial paresis
|
2.2%
1/45
|
|
Immune system disorders
Graft versus host disease
|
4.4%
2/45
|
|
Blood and lymphatic system disorders
Haemolysis
|
2.2%
1/45
|
|
Psychiatric disorders
Hallucination
|
2.2%
1/45
|
|
Nervous system disorders
Headache
|
2.2%
1/45
|
|
Hepatobiliary disorders
Hepatitis toxic
|
2.2%
1/45
|
|
Hepatobiliary disorders
Hepatomegaly
|
2.2%
1/45
|
|
Hepatobiliary disorders
Hepatotoxicity
|
4.4%
2/45
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.2%
1/45
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.2%
1/45
|
|
Vascular disorders
Hypertension
|
2.2%
1/45
|
|
Vascular disorders
Hypotension
|
2.2%
1/45
|
|
Investigations
Liver function test abnormal
|
2.2%
1/45
|
|
Nervous system disorders
Loss of consciousness
|
2.2%
1/45
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.2%
1/45
|
|
Gastrointestinal disorders
Nausea
|
2.2%
1/45
|
|
Cardiac disorders
Palpitations
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.2%
1/45
|
|
Infections and infestations
Pneumonia
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
2.2%
1/45
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
2.2%
1/45
|
|
General disorders
Pyrexia
|
4.4%
2/45
|
|
Renal and urinary disorders
Renal failure
|
2.2%
1/45
|
|
Infections and infestations
Sepsis
|
4.4%
2/45
|
|
Investigations
Sputum culture positive
|
2.2%
1/45
|
|
Cardiac disorders
Tachycardia
|
2.2%
1/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.2%
1/45
|
|
Vascular disorders
Venoocclusive disease
|
2.2%
1/45
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
3/45
|
|
Investigations
Weight increased
|
2.2%
1/45
|
Other adverse events
| Measure |
Voriconazole
n=45 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
15.6%
7/45
|
|
Gastrointestinal disorders
Abdominal pain upper
|
13.3%
6/45
|
|
Immune system disorders
Acute graft versus host disease
|
6.7%
3/45
|
|
Blood and lymphatic system disorders
Anaemia
|
15.6%
7/45
|
|
Metabolism and nutrition disorders
Anorexia
|
8.9%
4/45
|
|
Psychiatric disorders
Anxiety
|
6.7%
3/45
|
|
General disorders
Asthenia
|
8.9%
4/45
|
|
General disorders
Chills
|
11.1%
5/45
|
|
Hepatobiliary disorders
Cholestasis
|
6.7%
3/45
|
|
Immune system disorders
Chronic graft versus host disease
|
6.7%
3/45
|
|
Eye disorders
Conjunctivitis
|
6.7%
3/45
|
|
Gastrointestinal disorders
Constipation
|
11.1%
5/45
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
3/45
|
|
Infections and infestations
Cytomegalovirus infection
|
8.9%
4/45
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
15/45
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
3/45
|
|
Skin and subcutaneous tissue disorders
Erythema
|
11.1%
5/45
|
|
General disorders
Fatigue
|
8.9%
4/45
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
17.8%
8/45
|
|
Immune system disorders
Graft versus host disease
|
26.7%
12/45
|
|
Psychiatric disorders
Hallucination
|
6.7%
3/45
|
|
Nervous system disorders
Headache
|
28.9%
13/45
|
|
Hepatobiliary disorders
Hepatotoxicity
|
6.7%
3/45
|
|
Vascular disorders
Hypertension
|
17.8%
8/45
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
6.7%
3/45
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.7%
3/45
|
|
Psychiatric disorders
Insomnia
|
15.6%
7/45
|
|
Investigations
Liver function test abnormal
|
8.9%
4/45
|
|
General disorders
Mucosal inflammation
|
37.8%
17/45
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.7%
3/45
|
|
Gastrointestinal disorders
Nausea
|
11.1%
5/45
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
3/45
|
|
General disorders
Oedema peripheral
|
11.1%
5/45
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
3/45
|
|
General disorders
Pyrexia
|
28.9%
13/45
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
6/45
|
|
Infections and infestations
Sinusitis
|
6.7%
3/45
|
|
Psychiatric disorders
Sleep disorder
|
6.7%
3/45
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
15.6%
7/45
|
|
Gastrointestinal disorders
Vomiting
|
28.9%
13/45
|
|
Investigations
Weight decreased
|
6.7%
3/45
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER