Table 2.
Schedule of enrollment, interventions and assessments (SPIRIT figure)
| Study phase | Screening | Baselinea | Treatment | Follow-up | ||
|---|---|---|---|---|---|---|
| Visit procedures |
SCR Day − 28 to day 0 |
V1 Day 1 (diagnosis SSC) |
V2 Week 8 ± 5 days |
V3 Week 16 ± 5 days |
V4/UN/ET Week 24 (end of treatment) ± 5 days |
FU1-FU3 Every 8 weeks ± 5 days |
| Clinical assessment | ||||||
| Informed consent | x | |||||
| Eligibility criteria | x | |||||
| Gender and age | x | |||||
| Medical history | x | |||||
| ICU related history | x | |||||
| Vital signs and oxygen saturation | x | x | x | x | x | x |
| Height and skin color | x | |||||
| Weight | x | x | x | x | x | x |
| Concomitant medication | x | x | x | x | x | x |
| Pregnancy prevention counseling | x | x | x | x | x | |
| Endoscopic evaluation (ERC) | x |
x (intervention group) |
x (intervention group) |
x (intervention group or clinically necessary for UN/ET) |
||
| MRCPb | x | x | ||||
| Endoscopic intervention (ERC) |
x (endoscopic evaluation only at non-intervention group) |
x (intervention group) |
x (intervention group) |
x (intervention group or clinically necessary for UN/ET) |
||
| Randomization | x | |||||
| Checking the components of the primary endpointc | x | x | x | x | ||
| Secondary endpointsd | x | |||||
| SOFA score | x | x | x | x | x | |
| Serious adverse events | x | x | x | x | x | |
| Laboratory assessment | ||||||
| Hematology | x | x | x | x | x | x |
| Serum chemistry | x | x | x | x | x | x |
| Thyroid function test | x | |||||
| Serum or urine ß-hCG pregnancy testinge | x | x | x | x | x | |
| Genetic sample | x | |||||
| Serum/plasma | x | x | x | x | x | x |
| Bile specimen | x |
x (intervention group) |
x (intervention group) |
x (intervention group or clinically necessary for UN/ET) |
||
aBaseline/day 1 assessments must be performed prior to treatment
bMRCP at screening if possible. MRCP at visit 4 may only be performed if MRCP has been conducted during screening (not for unscheduled visit (UN), preferably prior to ERC)
cThe primary endpoint is defined as occurrence of death or necessity of liver transplantation or occurrence of cholangiosepsis, whatever occurs first
dSecondary endpoints: single components of the primary endpoint: liver transplantation, death, cholangiosepsis; Laboratory parameters (bilirubin, AP, GGT, AST, ALT, LDH, GLDH, creatinine, CRP, CHE) as change from baseline; model for end-stage liver disease score (MELD) score as change from baseline; unplanned hospital admissions (necessity and days free of hospital care within 6 months); unplanned intensive care unit (ICU) admissions (necessity and days free of intensive care unit care, invasive ventilation, renal replacement therapy, vasopressors within 6 months), necessity of anti-infective treatment
eSerum pregnancy testing at screening and urine pregnancy testing during the study for females of childbearing potential only (if urine pregnancy testing is positive, a confirmation with serum pregnancy testing is required)