AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial

Table 1 Schedule of enrolment, interventions and assessments adapted from the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure

	Screening	Week 1							Week 2							Week 4	Week 6	Week 8	Week 10	Week 16
Study day	≤D0	D1	D2	D3	D4	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14	Week 4	Week 6	Week 8	Week 10	Week 16
Consent and randomisation
Eligibility criteria	X	X
PIS and signed consent	X	X
Randomisation	X	X
Treatment
Intervention: Ambisome 10 mg/kg		X
Intervention: Fluconazole 1200 mg/day		X	X	X	X	X	X	X	X	X	X	X	X	X	X
Intervention: Flucytosine 100 mg/kg/day		X	X	X	X	X	X	X	X	X	X	X	X	X	X
Control: Amphotericin B deoxycholate 1 mg/kg		X	X	X	X	X	X	X
Control: Flucytosine 100 mg/kg/day		X	X	X	X	X	X	X
Control: Fluconazole 1200 mg/day									X	X	X	X	X	X	X
All participants: Fluconazole 800 mg/day															X	X	X	X	X
All participants: 200 mg/day																			X	X
Clinical, safety and compliance assessment
Inpatient clinical review		X	X	X	X	X	X	X	X	X	X	X	X	X	X
Outpatient follow-up																X	X	X	X
Week 16 telephone																				X
Clinical labs
HIV testing		X
Pregnancy test (urine/serum)^a		X
Full blood count		X						X							X	X
CD4 count		X
ALT		X						X							X	X
Urea, creatinine and electrolytes		X		X		X		X			X		X		X	X
Drug levels		X						X
Quantitative PCR sub-study		X		X				X							X
Semi-quantitative cryptococcal antigen		X
CSF
Opening pressure		X						X							X
Cell count and differential^b		X
Protein, glucose^b		X
Routine culture^b		X
India ink examination^b,c		X
Cryptococcal antigen^b,c		X
Quantitative fungal culture		X						X							X
CSF drug levels		X						X							X
Immune parameters		X						X							X
Semi-quantitative cryptococcal antigen		X

^aFor women of childbearing age; ^bPart of routine care; ^cIndia ink or cryptococcal antigen required for inclusion

ISSN: 1745-6215