Table 5. In-patient schedule of events.
| Study visit | Screening | Enrolment D1 | Day 2 | Day 3 | Day 7 | Day 10 | Day 14 | Further
Hospitalization |
|---|---|---|---|---|---|---|---|---|
| Visit window (days) | ±1 | ±1 | ±1 | ±1 | ±2 | |||
| Screening Consent | X | |||||||
| Assess eligibility criteria | X | |||||||
| Informed enrolment consent | X | |||||||
| Clinical history and examination | ||||||||
| Past medical history | (X) | |||||||
| Medication review | (X) | X | X | X | X | X | X | X |
| Document HIV status | (X) | |||||||
| Current symptoms | (X) | X | X | X | X | X | X | X |
| Examination | (X) | X | X | X | X | X | X | X |
| GCS score | (X) | X | X | X | X | X | X | X |
| BMRC disease grade | X | X | X | X | X | X | X | |
| Adverse events assessment b | X | X | X | X | X | X | X | |
| Investigations | ||||||||
| HIV-test (if not known positive) | (X) | |||||||
| Cryptococcal antigen | (X) | |||||||
| Sodium/Potassium | X i | X i | X | X | X | |||
| Glucose (bedside) | (X) | |||||||
| Creatinine h | X i | X i | X | X | X | |||
| Hepatic panel a | X i | X i | X | X | X | X | ||
| Blood Count (including differential) | X i | X i | X | X | ||||
| CD4 count if HIV-positive | X i | X i | ||||||
| Pregnancy test | Women | |||||||
| CSF sample (aim >10ml, as per SOP c) | (X) | X d | as clinically indicated
(storage of remaining specimen) |
X
(Paired plasma) |
X
(as clinically indicated) |
|||
| Plasma PK sampling 0, 2, 4, 8 hrs | X | |||||||
| Sparse plasma PK (one sample) | X | |||||||
| Chest radiograph | (+/-) | |||||||
| CT head f | +/- | +/- | ||||||
| Abdominal Ultrasound Scan | X | |||||||
| Urine sample g | (X) | |||||||
| Blood/DNA/RNA storage | with consent | with consent | ||||||
| Approx. volume blood (mL) | 0 | 20 | 20 | 3 | 7 | 0 | 7 | 7 |
()= part of routine medical care
a Hepatic panel = alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Hepatitis BsAg, Hepatitis C Ab and INR will be added if baseline ALT is elevated. In the event of DILI hepatic panel will be performed more regularly.
b Adverse events will be recorded according to DAIDS toxicity scale
c SOP = standard operating procedure detailing exact processing and testing algorithm of CSF
d CSF PK will be timing randomised to early (2–4hrs) or medium (4–6hrs) or late interval (6–8hrs) post dose.
f Contrast enhanced CT head is indicated if there is focal neurology at baseline or during enrolment period
g Urine sample may be collected for testing with LAM (lipoarobinmannan) or urine Xpert MTB/Rif Ultra as part of TB work-up
h Additional renal monitoring will be undertaken in those with abnormal baseline creatinine
i Baseline bloods must occur at either screening or enrolment visit. It is likely these visits will be on the same day. If baseline bloods were done at screening and enrolment occurs >48 hours later baseline blood tests will be repeated.