Table 1.
Characteristics of included trials
| Characteristic | Value (n = 101) |
|---|---|
| Journal, no. (%) | |
| New England Journal of Medicine | 48 (47.5%) |
| JAMA | 18 (17.8%) |
| Critical Care Medicine | 13 (12.9%) |
| American Journal of Respiratory and Critical Care Medicine | 6 (5.9%) |
| Intensive Care Medicine | 6 (5.9%) |
| Lancet | 6 (5.9%) |
| Lancet Respiratory Medicine | 4 (4.0%) |
| Main source of funding, no. (%)1 | |
| Government outside US | 54 (53.5%) |
| Industry | 23 (22.8%) |
| Non-profit organization | 11 (10.9%) |
| US government | 8 (7.9%) |
| Local institution | 5 (5.0%) |
| Geographic region(s) in which trial conducted, no. (%) | |
| Europe | 75 (74.3%) |
| US | 27 (26.7%) |
| Canada | 23 (22.8%) |
| Australia and/or New Zealand | 19 (18.8%) |
| Asia | 22 (21.8%) |
| Central or South America | 10 (9.9%) |
| Africa | 6 (5.9%) |
| Topic of trial, no. (%) | |
| Sepsis or infection | 34 (33.7%) |
| Respiratory | 21 (20.8%) |
| Cardiovascular | 19 (18.8%) |
| General critical care | 14 (13.9%) |
| Renal | 5 (5.0%) |
| Trauma | 4 (4.0%) |
| Other2 | 4 (4.0%) |
| Trial design, no. (%) | |
| Two-arm parallel group | 84 (83.2%) |
| Three-arm parallel group3 | 8 (7.9%) |
| Factorial 2×24 | 9 (8.9%) |
| Trial stopped early, no. (%)5 | 35 (34.7%) |
| Sample size in final analysis, median (IQR) | 843 (411–1588) |
| Main endpoint, no. (%) | |
| ≤ 7-day mortality | 3 (3.0%) |
| 28-day or 30-day mortality | 63 (62.4%) |
| 60-day or 90-day mortality | 23 (22.8%) |
| ≥ 180-day mortality | 3 (3.0%) |
| In-hospital mortality without specified interval | 9 (8.9%) |
| P-value ≤ 0·05 for primary endpoint, no. (%) | 12 (11.9%) |
| Significant benefit with intervention | 7 (6.9%) |
| Significant harm with intervention | 5 (5.0%) |
For studies with multiple funding sources, the primary funding source was considered governmental whenever the government was a trial sponsor regardless of other funding sources reported.
For all analyses, the five three-arm parallel group trials were handled as two-arm trials. One trial merged two groups in the main analysis. Two trials stopped enrollment in one arm early and reported as the main result a two-group comparison. Two trials explicitly stated the a priori main analysis consisted of two-group comparison without consideration for the third study arm.
Eight trials of factorial 2×2 design, reported in four publications, specified pairwise comparison of both factors in the main analysis. One trial of factorial 2×2 design specified comparing only one factor in the main analysis.
Reasons for trials stopping early included futility (n = 17), harm (n = 10), poor enrollment (n = 6), sponsor termination (n = 1), and drug/device withdrawal from market (n = 1).