TABLE 1.
Baseline demographics and clinical characteristics in the terlipressin group of the ITT populationa
| Baseline Serum Creatinine Subgroup (N=352) | ||||
|---|---|---|---|---|
| Parameters | <3 mg/dL (n=126) | ≥3–<5 mg/dL (n=182) | ≥5 mg/dL (n=44) | p b |
| Age, years | ||||
| Median | 56.8 | 54.2 | 56.2 | 0.27 |
| Minimum, maximum | 26.8, 73.7 | 23.2, 78.0 | 26.7, 77.0 | |
| Sex | ||||
| Male | 74 (58.7) | 111 (61.0) | 28 (63.6) | 0.85 |
| Female | 52 (41.3) | 71 (39.0) | 16 (36.4) | |
| Baseline serum creatinine, mg/dL | ||||
| Median | 2.6 | 3.6 | 5.6 | |
| Minimum, maximum | 1.7, 3.0 | 3.0, 4.9 | 5.0, 11.9 | |
| Baseline MELD score | ||||
| n | 113 | 158 | 41 | <0.001 |
| Median | 31.0 | 35.5 | 38.0 | |
| Minimum, maximum | 16.0, 40.0 | 20.0, 40.0 | 21.0, 40.0 | |
| Child-Pugh Class C | 84 (66.7) | 121 (66.5) | 27 (61.4) | 0.79 |
| International normalized ratio | ||||
| n | 118 | 166 | 41 | 0.83 |
| Median | 2.1 | 2.1 | 2.0 | |
| Minimum, maximum | 1.2, 5.2 | 1.0, 5.8 | 1.1, 3.9 | |
| MAP (mm Hg) | ||||
| Median | 77.8 | 75.2 | 75.7 | 0.20 |
| Minimum, maximum | 52.3, 106.7 | 47.0, 117.7 | 53.3, 100.7 | |
| Lab parameters | ||||
| Albumin (g/dL) | ||||
| n | 121 | 170 | 42 | 0.61 |
| Median | 3.6 (0.76) | 3.4 (0.82) | 3.6 (1.01) | |
| Minimum, maximum | 1.5, 5.3 | 1.2, 5.1 | 1.8, 5.8 | |
| Sodium (mmol/L) | ||||
| n | 125 | 180 | 44 | 0.91 |
| Median | 133 | 132.0 | 133 | |
| Minimum, maximum | 115.0, 154.0 | 116.0, 150.0 | 114.0, 148.0 | |
| Total bilirubin (mg/dL) | ||||
| n | 122 | 173 | 43 | 0.39 |
| Median | 6.1 | 7.1 | 10.8 | |
| Minimum, maximum | 0.4, 51.6 | 0.3, 50.4 | 0.7, 46.7 | |
| History of infections | ||||
| Spontaneous bacterial peritonitis | 22 (20.4) | 19 (12.4) | 4 (11.4) | 0.19 |
| Urinary tract infection | 20 (18.5) | 30 (19.6) | 7 (20.0) | 0.96 |
| Pneumonia | 8 (7.4) | 11 (7.2) | 2 (5.7) | 1.00 |
| Other | 19 (17.6) | 30 (19.6) | 6 (17.1) | 0.59 |
| Ascitesc grade 3 | 50 (39.7) | 66 (36.3) | 20 (45.5) | 0.51 |
| Alcoholic hepatitis | 42 (33.3) | 60 (33.0) | 19 (43.2) | 0.43 |
| Alcoholic hepatitis, baseline MAP <70 mm Hg, or SIRS | 82 (65.1) | 121 (66.5) | 30 (68.2) | 0.93 |
| Esophageal varices | ||||
| Prior history of esophageal variceal hemorrhage | 17 (13.5) | 32 (17.6) | 7 (15.9) | 0.45 |
| Precipitating factors for HRS-1 | 50 (39.7) | 80 (44.0) | 19 (43.2) | 0.77 |
| Prior midodrine and octreotide, ≥3 d | 33 (26.2) | 39 (21.4) | 12 (27.3) | 0.54 |
| SIRS subgroupd | 41 (38.0) | 55 (35.9) | 16 (45.7) | 0.72 |
| Baseline ACLF grade | 0.36 | |||
| 0 | 2 (1.6) | 0 | 0 | |
| 1 | 64 (50.8) | 82 (45.1) | 16 (36.4) | |
| 2 | 38 (30.2) | 61 (33.5) | 17 (38.6) | |
| 3 | 22 (17.5) | 39 (21.4) | 11 (25.0) | |
| Daily exposure to terlipressin (mg/d), median (minimum, maximum) | 3.3 (0.9, 7.2) | 3.2 (0.8, 7.1) | 3.0 (1.0, 6.9) | 0.22 |
| Prior albumin exposure (g) | ||||
| n | 114 | 161 | 37 | 0.62 |
| Median | 300.0 | 300.0 | 300.0 | |
| Minimum, maximum | 25.0, 925.0 | 25.0, 1000.0 | 50.0, 800.0 | |
| Daily concomitant albumin exposure (g/dL) | ||||
| n | 99 | 164 | 36 | 0.15 |
| Median | 45.0 | 46.7 | 50.0 | |
| Minimum, maximum | 12.5, 150.0 | 12.5, 150.0 | 12.5, 100.0 | |
Data are presented as n (%) unless otherwise stated.
Pooled data were collated from the following Phase III studies: OT-0401, REVERSE, and CONFIRM.
The p values for continuous variables were based on a comparison of baseline serum creatinine categories using the Kruskal-Wallis test; for categorical variables, a Fisher exact test or χ2 test were used.
Every patient had to have a documented history of cirrhosis and ascites to be eligible for the clinical studies in the pooled ITT population.
Criteria to define the SIRS subgroup were not collected for OT-0401; percentages are based on the number of patients in each treatment group for REVERSE and CONFIRM only (<3 mg/dL, n=108, ≥3–<5 mg/dL, n=153; ≥5 mg/dL, n=35).
For patients who received albumin during initial and retreatment periods, albumin exposure data were combined for both periods. Records missing the albumin dose or the date of dosing were excluded.
Abbreviations: ACLF indicates acute-on-chronic liver failure; d, day; HRS-1, hepatorenal syndrome type 1; ITT, intent-to-treat; MAP, mean arterial pressure; max, maximum; MELD, model for end-stage liver disease; min, minimum; n, number of patients; SIRS, systemic inflammatory response syndrome.