Introduction
Materials and methods
Study design
Study participants
DNAemia
Randomization
Study interventions
Study outcomes
Data safety monitoring board
Statistical analysis
Results
Characteristics | Placebo group (N = 37) | Ganciclovir group (N = 39) |
---|---|---|
Age, y | 67.0 (59.0–72.0) | 63.0 (54.0–71.0) |
Male sex, no. (%) | 25 (67.6) | 31 (79.5) |
Body mass index, kg/m2a | 27.7 (21.3–31.2) | 26.2 (23.6–35.2) |
McCabe score = 1 (non-fatal), no. (%) | 32 (86.5) | 28 (71.8) |
Preexisting disease, no. (%) | ||
NYHA III/IV | 4 (10.8) | 3 (7.7) |
Cancer/hemopathy | 3 (8.1) | 7 (17.9) |
Diabetes mellitus | 6 (16.2) | 10 (25.6) |
COPD | 4 (10.8) | 7 (17.9) |
Cirrhosis | 3 (8.1) | 0 (0) |
Chronic renal failure a | 1 (2.7) | 2 (5.1) |
Alcoholism, no. (%) | 6 (16.2) | 5 (12.8) |
Recent transfusion (< 1 month), no. (%) | 12 (32.4) | 13 (33.3) |
Corticosteroids (< 1 month), no. (%) | 5 (13.5) | 1 (2.6) |
No preexisting disease and no risk factor, no. (%) | 17 (45.9) | 16 (41) |
Admission category, no. (%) | ||
Medical | 31 (83.8) | 34 (87.2) |
Emergency surgery | 2 (5.4) | 4 (10.3) |
Planned surgery | 4 (10.8) | 1 (2.8) |
Primary reason for mechanical ventilation, no. (%) | ||
Acute respiratory failure | 13 (35.1) | 12 (30.8) |
Septic shock | 8 (21.6) | 8 (20.5) |
Cardiogenic shock | 2 (5.4) | 5 (12.8) |
Post-operative acute respiratory failure | 4 (10.8) | 1 (2.6) |
Exacerbation of chronic respiratory disease | 0 (0) | 4 (10.3) |
Trauma | 1 (2.7) | 0 (0) |
Neurologic | 1 (2.7) | 1 (2.6) |
Cardiac arrest | 1 (2.7) | 0 (0) |
Others | 7 (18.9) | 8 (20.5) |
SAPS II | 45.0 (38.5–56.5) | 45.0 (37.0–59.0) |
SOFA score | 10 (8–15) | 9 (7–10) |
Organ/system failure, no. (%)b | ||
Cardiovascular | 23 (62.2) | 28 (71.8) |
Respiratory | 26 (81.2) | 29 (80.6) |
Renal | 11 (29.7) | 11 (28.2) |
Central nervous | 8 (21.6) | 1 (2.6) |
Hepatic | 1 (2.8) | 2 (5.3) |
Coagulation | 4 (10.8) | 2 (5.1) |
Characteristics | Placebo group (N = 37) | Ganciclovir group (N = 39) |
---|---|---|
Ongoing antimicrobial treatment, no. (%) | 26 (70.3) | 28 (71.8) |
ECMO use, no. (%) | 5 (13.5) | 6 (15.4) |
Renal replacement therapy, no. (%) | 14 (37.8) | 13 (33.3) |
SOFA score | 8.0 (5.0–11.0) | 8.5 (4.0–10.3) |
Organ/system failure, no. (%)a | ||
Cardiovascular | 18 (48.6) | 19 (48.7) |
Respiratory | 22 (59.5) | 24 (61.5) |
Renal | 12 (32.4) | 14 (35.9) |
Central nervous | 6 (16.2) | 4 (10.3) |
Hepatic | 2 (5.4) | 3 (7.9) |
Coagulation | 2 (5.4) | 2 (5.1) |
Body temperature, ℃ | 37.7 (36.3–38.2) | 37.8 (36.9–38.3) |
White blood-cell count, G/L | 13.6 (10.2–17.8) | 14.0 (10.2–20.0) |
Neutrophil count, G/L | 11.4 (7.5–15.6) | 10.7 (7.1–16.0) |
PaO2/FiO2, mmHg | 175.0 (127.5–237.0) | 170.0 (111.0–240.0) |
Radiologic score | 6.0 (4.0–8.5) | 5.5 (3.0–8.0) |
Tidal volume, mL | 450.0 (390.3–554.3) | 448.0 (370.5–497.0) |
Respiratory rate, cycles/min | 28.0 (20.0–33.0) | 25.0 (22.0–29.3) |
Minute ventilation, L/min | 12.0 (9.2–14.9) | 10.4 (8.7–13.9) |
PEEP, cmH2O | 8.0 (5.0–10.0) | 8.0 (6.0–12.0) |
Plateau pressure, cmH2O | 19.0 (15.0–26.0) | 22.0 (17.3–26.5) |
FiO2, % | 40.0 (30.0–50.0) | 40.0 (35.0–55.0) |
pH | 7.43 (7.36–7.48) | 7,42 (7.37–7.48) |
PaO2, mmHg | 85.0 (70.5–102.0) | 81.0 (67.5–115.0) |
PaCO2, mmHg | 35.0 (33.0–41.0) | 40.5 (35.0–45.3) |
Study drug
Parameters | Placebo group (N = 37) | Ganciclovir group (N = 39) | P Value |
---|---|---|---|
Primary outcome | |||
Ventilator-free days on day 60 | 0 (0–43) | 10 (0–51) | 0.459 |
Secondary outcomes (post-randomization) | |||
Day-60 mortality, no. (%) | 16 (43.2) | 16 (41.0) | 0.845 |
Duration of MV | 20 (7–40) | 12 (6–29) | 0.246 |
ICU length of stay (from admission) | 44.0 (21.0–66.5) | 36.0 (24.0–51.0) | 0.377 |
ICU length of stay (from randomization) | 26.0 (11.0–50.0) | 17.0 (8.0–34.0) | 0.318 |
Hospitalization length (from admission) | 60.0 (33.0–75.5) | 65.0 (28.0–78.0) | 0.988 |
Hospitalization length (from randomization) | 42.0 (18.5–60.0) | 38.0 (13.0–60.0) | 0.945 |
HSV bronchopneumonitis, no. (%) | 1 (2.7) | 0 (0) | 0.487 |
Cytomegalovirus infection, no. (%) | 5 (13.5) | 1 (2.6) | 0.103 |
Ventilator-associated pneumonia, no. (%) | 15 (40.5) | 13 (33.3) | 0.515 |
Secondary bacteremia or fungemia, no. (%) | 8 (21.6) | 7 (17.9) | 0.688 |
ARDS post-randomization, no. (%) | 6 (16.2) | 6 (15.4) | 0.921 |
Milda | 0 | 0 | |
Moderatea | 3 | 3 | |
Severea | 3 | 3 | |
Septic shock post-randomization, no. (%) | 14 (37.8) | 13 (33.3) | 0.682 |
Renal replacement therapy until day 28, no. (%) | 18 (48.6) | 16 (41.0) | 0.504 |
Number of days with study drug, no. (%) | 14 (7.5–14) | 14 (6.0–14) | 0.991 |