Arathoon 2002.

Methods	A Multi‐centre, single country study conducted in South America. Dates of enrolment and completion of study not reported. Analysis: no ITT
Participants	Eligibility criteria: patients who had oropharyngeal and/ oesophageal candidiasis Exclusion criteria: Pregnant, breast feeding, inadequate contraception, allergy or serious adverse event to glucan synthesis inhibitors or amphotericin B, previous failure with amphotericin B treatment, ongoing treatment with rifampicin or ritonavir, any underlying condition that deemed likely to confound interpretation of results or pose undue risk to the patient, abnormal laboratory results: hematocrit =< 27%; absolute neutrophil count < 1,000/ul; platelet count <= 75,000/ul; creatinine clearance < 50ml/min; prothrombin time > upper limit of normal and / or total bilirubin > 3 or more times upper limit of normal; ALT or AST > 5 or more times upper limit of normal Diagnosis confirmed by visualisation of Candida pseudohyphae in appropriate specimens. 140 patients enrolled C1=34 C2=34 C3=37 A1=35
Interventions	C1 ‐ caspofungin acetate 35 mg C2 ‐ caspofungin acetate 50 mg C3 ‐ caspofungin acetate 70 mg plus placebo A1 ‐ amphotericin B (0,5mg/kg) or placebo intravenously, once daily Patients were randomly allocated to one of four interventions and stratified according to presentation with either oropharyngeal infection alone or esophageal disease with or without oropharyngeal involvement. Patients were further subdivided according to previous refractory (S1) or responsive (S2) fluconazole therapy. Treatment duration: minimum 7 days, maximum of 14 days
Outcomes	Primary end point: Combined response of referable symptoms and visible lesions assessed 3‐4 days after discontinuation of study drug. Relapse: Recurrence of symptoms or signs of Candida infection during the month after discontinuation of therapy Microbiological eradication: Culture results 3‐4 days after discontinuation of therapy Adverse events: significantly fewer C recipients developed drug‐related fever, chills, nausea or vomiting. Incidence of local reactions (infusion related) ranged from 6‐14% across treatment arms. Drug related laboratory abnormalities (raised ALT, AST, ALP, Creatinine, and decreased K) were also more common in patients taking amphotericin B.
Notes	Ethics: IRB approved protocol and informed consent obtained 3 patients not HIV + Author contacted to clarify treatment allocation, allocation concealment, and blinding. No response to date 11/11/2004
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	No description given of how sequence generation was done
Allocation concealment?	Unclear risk	Not reported
Blinding? All outcomes	Unclear risk	Mention that double blinding was used but unclear who was blinded
Incomplete outcome data addressed? All outcomes	Low risk	Drop‐outs clearly described Loss to follow‐up: unclear how many patients completed treatment