Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00624143 |
| Other study ID # |
antifungal prophylaxis |
| Secondary ID |
Dr. SAMEER BAKHS |
| Status |
Recruiting |
| Phase |
Phase 3
|
| First received |
February 19, 2008 |
| Last updated |
February 19, 2008 |
| Start date |
February 2008 |
Study information
| Verified date |
January 2008 |
| Source |
All India Institute of Medical Sciences, New Delhi |
| Contact |
SAMEER BAKHSHI, MD |
| Phone |
91-11-26588153 |
| Email |
sambakh[@]hotmail.com |
| Is FDA regulated |
No |
| Health authority |
India: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
Hypothesis:Oral Voriconazole will be as effective as intravenous Amphotericin B as
antifungal prophylaxis in induction of acute leukemia (ALL, AML) in pediatric patients, with
less toxicity and more convenience.
Description:
RATIONALE OF STUDY:
- In induction chemotherapy for childhood acute leukemia, our experience and
international studies has shown that 30% of ALL and approximately 50% of AML patients
require antifungal therapy. Mortality rates associated with documented fungal infection
due to opportunistic yeasts and filamentous fungi have been high, ranging from 50-90%
despite use of therapeutic amphotericin B or voriconazole.
- Currently licensed drug for use in pediatric patients are amphotericin B and its lipid
derivatives; 5-flucytosine; azoles like fluconazole, itraconazole, voriconazole; and
caspofungin.
- Limitation with Fluconazole- inactive against Aspergilosis, C. glabrata, C. krusei, C.
parapsilosis and filamentous fungi.
- Limitation with Itraconazole- erratic oral absorption of capsule form, frequent drug
interactions, non availability of oral suspension form for use in very small children
who would not be able to take capsules.
- Amphotericin B and Voriconazole both have proven activity against filamentous fungi and
candida species.
- There is no prospective, randomised trial comparing voriconazole and amphotericin B in
prophylaxis of pediatric acute leukemia during induction.
Hence there is need to study their role in prophylaxis of this infection which has a high
mortality despite therapy.
Study design: Prospective, Randomized, concealed, single institutional study.
Study population:
Pediatric patients of acute leukaemia who undergo induction chemotherapy at IRCH between Jan
2008 to Dec 2009 will be eligible for the study.
Inclusion criteria:
- Patients age less than or equal to 15 years with de novo acute leukemia undergoing
induction chemotherapy.
- No evidence of fungal infection at randomization
- No pneumonia at presentation.
- No systemic antifungal therapy within 7 days before randomization.
Febrile patients with no pneumonia, systemic fungal infection and hemodynamically stable
will be eligible for study.
Exclusion criteria:
- Patients with baseline pneumonia.
- Laboratory evidence of significant hepatic or renal dysfunction (defined as a SGOT or
SGPT more than 5 times, Total bilirubin more than 2 times and Serum creatinine more
than 2 times upper limit of normal)
End points:
- Proven or probable invasive fungal infection.
- Initiation of full dose parental antifungal therapy for proven or probable invasive
fungal infection.
- Successful recovery of ANC more than 1000/cumm or completion of induction.
Study protocol:
- After signing informed consent forms patients will be randomly assigned to a regimen of
oral Voriconazole or IV low dose Amphotericin B.
- Oral Voriconazole will be given in dose of 6mg/kg 12 hourly on day1 then 4mg/kg 12
hourly daily or IV Amphotericin B 0.5 mg/kg/day weekly thrice.
- Patient will be started at the time of initiation of induction till completion of
induction.
Evaluation:
- Patients will be evaluated at baseline, twice weekly for duration of study and at
completion of study.
Baseline evaluation:
- History and physical examination.
- Hemogram and biochemistry
- Chest X ray
Evaluation of patients with baseline fever:
For the patient presenting with fever at baseline (randomization), blood and urine culture
for fungus and bacteria will be send, X- ray chest to rule out consolidation at baseline
will be done in all patients. The patients will be started on antibiotics as per the routine
institutional policy. If patient becomes afebrile before day 5, then antibiotics will be
continued for 5 days after becoming afebrile. If patient is still febrile at day 5, then
empiric therapeutic antifungal therapy will be added.
Evaluation of patients with breakthrough fever:
In case of patient developing fever >38 degree C (axillary) during induction chemotherapy,
patient will be evaluated by clinical examination, hemogram ,biochemistry, chest X ray,
blood and urine culture for fungus and bacterial for three consecutive days. Patients with
evidence of chest infection on chest X ray/signs and symptoms of chest infection/febrile
even after receiving 5 days of appropriate antibiotics will be subjected to HRCT scan of
chest. Patients showing consolidation , or signs of chest infection on chest CT will be
subjected for broncoscopy and bronchoalveolar lavage. The brochoalveolar lavage will be sent
for microscopy (gram staining), culture for fungal and bacterial growth. Full dose
therapeutic antifungal will be started earlier in case of development of pneumonia,
hemodynamic instability even if before 5 days of antibiotics which will be considered as
failure of prophylaxis. Whenever feasible (not mandatory) depending on the patient's
clinical condition, we will try to obtain tissue sample for histology by FNAC/Biopsy from
the suspected infected site.
