Acute Respiratory Failure
Conditions
Brief summary
This is a phase 3 study designed to evaluate whether the administration of ganciclovir increases ventilator-free days in immunocompetent patients with sepsis associated acute respiratory failure. Our hypothesis is that IV ganciclovir administered early in critical illness will effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory failure thereby leading to improved clinical outcomes
Interventions
DRUGIV Ganciclovir
For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.
DRUGNormal saline
For first 5 days, dosing of intravenous saline is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV saline 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject/next of kin informed consent * Age \> 18 years * CMV IgG seropositive by lateral flow assay (LFA) or standard serologic methods * Receiving care in an ICU * Acute respiratory failure as defined in Section 4.1.1. * Expected to require respiratory support for at least 2 more days after randomization * Infection confirmed or suspected by the treating clinician and felt to be the source of acute respiratory failure (Respiratory failure associated with infection confers at least 2 SOFA points above assumed baseline SOFA score of 0, thereby meeting Sepsis-3 definition).
Exclusion criteria
* Known or suspected immunosuppression, including: * HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment) * stem cell transplantation: * within 6 months after autologous transplantation or * within 1 years after allogeneic transplantation (regardless of immunosuppression) * greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease) Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization. * solid organ transplantation with receipt of systemic immunosuppression (any time) * cytotoxic anti-cancer chemotherapy within the past three months (Note: next-of-kin estimate is acceptable) * congenital immunodeficiency requiring antimicrobial prophylaxis (e.g. TMP-SMX, dapsone, antifungal drugs, intravenous immunoglobulin) * receipt of one or more of the following in the indicated time period (see Appendix C): * within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies, or other immunosuppressive drugs associated with CMV reactivation Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix C for commonly prescribed immunosuppressive agents. Information on the use of biologics with moderate immunosuppressive effect but no known effect on CMV are permitted and will be recorded in the CRFs. * Expected to survive \< 72 hours (in the opinion of the investigator) * Has been hospitalized for \> 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable). * Pregnant or breastfeeding (either currently or expected within one month). Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization \[hysterectomy, tubal ligation, oophorectomy\]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable. * Absolute neutrophil count \< 1,000/mm3 (if no ANC value is available, the WBC must be \> 2500/mm3) * Use of anti-CMV drugs (cidofovir, letermovir, foscarnet, valganciclovir, ganciclovir) within seven (7) days of patient randomization. * Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity or to be associated with significant known hematologic toxicity (prior approval required). * At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation. * Patients with Child Class C Cirrhosis. * Patients with severe (requiring home oxygen) pre-existing interstitial lung disease. * Allergy to ganciclovir * Incarcerated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure | up to 28 days | To evaluate whether administration of ganciclovir increases respiratory-support-free days in immunocompetent patients with sepsis-associated acute respiratory failure. The outcome is the number of days the participant is not on respiratory support in the first 28 study days. This outcome uses the last-off approach to calculate the number of respiratory support days. The number of support days after calculated from the last day the participant was on respiratory support. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure. | up to 28 study days | During the first 28 study days, the number of days the participants are not on mechanical ventilation using the last off approach is compared between the two treatment arms. |
| To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure | up to 28 days | During the first 28 study days, the number of days the participants are not on any respiratory-support is compared between the two treatment arms. Instead of using last-off approach, we will count all the days during 28 days period. |
| To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | at study day 28 | This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at 28 days. The hazard ratio and Cox proportional hazards models are used for this endpoint. |
| To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | at the final study visit (day 180) | This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at the end of the study (day 180). |
| To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients. | up to 28 days | During the first 28 study days, the number of days the participants are not in ICU using the last off approach is compared between the two treatment arms. |
| To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | up to 28 days | This endpoint summarizes the days of all types of respiratory support for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded. |
| To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | up to 7 days | The PaO2/FiO2 (P/F) ratio was used to define oxygenation. The P/F ratio was summarized over the first 7 days of the study. The lowest PaO2 value within each study day was reported and used in the oxygenation calculation. If the PaO2 value was not available, an estimate of PaO2 was calculated from the SpO2 lowest value. |
| To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | up to 28 days | CMV DNA detection in plasma and endotracheal aspirate (ETA) by day 28 is defined as positive CMV PCR result from any ETA, plasma, or serum specimen collected through day 28. CMV reactivation by day 28 will be summarized with number of participants with CMV reactivation in two levels: as any detectable CMV DNA (any level) and as high-level reactivation (\>1000 IU/mL) for CMV negative patients at baseline. |
| To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups. | up to 28 days | During the first 28 days, this endpoint summarizes the number of participants who experienced adverse events (AEs) of severity grade ≥3 and whether any serious adverse events (SAEs) occurred in each study arm. |
| To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | up to 28 days | This endpoint summarizes the days of mechanical ventilation for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded. |
Countries
United States
Participant flow
Recruitment details
205 participants were enrolled at 19 U.S. clinical sites from June 29, 2021 until September 27, 2024 when the DSMB recommended early study closure.
Pre-assignment details
205 participants met the eligibility criteria. They were enrolled and randomized to study treatment simultaneously.
Participants by arm
| Arm | Count |
|---|---|
| IV Ganciclovir 5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge
IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose. | 106 |
| Placebo normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge
Placebo: For first 5 days, dosing of intravenous saline is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV saline 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose. | 99 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 45 | 22 |
| Overall Study | Lost to Follow-up | 13 | 12 |
| Overall Study | Patient or LAR refuses further participation | 0 | 3 |
| Overall Study | Unable to adhere | 0 | 2 |
| Overall Study | Withdrawal of consent | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | IV Ganciclovir | Total |
|---|---|---|---|
| Age, Continuous | 59 years | 63 years | 62 years |
| Age, Customized 18 - 20 | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 21 - 30 | 7 Participants | 5 Participants | 12 Participants |
| Age, Customized 31 - 40 | 11 Participants | 8 Participants | 19 Participants |
| Age, Customized 41 - 50 | 14 Participants | 13 Participants | 27 Participants |
| Age, Customized 51 - 60 | 21 Participants | 21 Participants | 42 Participants |
| Age, Customized 61 - 70 | 24 Participants | 27 Participants | 51 Participants |
| Age, Customized 71 - 80 | 16 Participants | 28 Participants | 44 Participants |
| Age, Customized 81 + | 6 Participants | 4 Participants | 10 Participants |
| CoVID Infected No | 82 Participants | 97 Participants | 179 Participants |
| CoVID Infected Yes | 17 Participants | 9 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 84 Participants | 92 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 7 Participants | 18 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 20 Participants | 21 Participants | 41 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 10 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized White | 68 Participants | 77 Participants | 145 Participants |
| Respiratory Support Missing | 0 Participants | 0 Participants | 0 Participants |
| Respiratory Support On HFNC | 21 Participants | 20 Participants | 41 Participants |
| Respiratory Support On mechanical ventilation | 75 Participants | 81 Participants | 156 Participants |
| Respiratory Support On NIV | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 56 Participants | 53 Participants | 109 Participants |
| Sex: Female, Male Male | 43 Participants | 53 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 45 / 106 | 22 / 99 |
| other Total, other adverse events | 22 / 106 | 18 / 99 |
| serious Total, serious adverse events | 0 / 106 | 0 / 99 |
Outcome results
Primary
Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure
To evaluate whether administration of ganciclovir increases respiratory-support-free days in immunocompetent patients with sepsis-associated acute respiratory failure. The outcome is the number of days the participant is not on respiratory support in the first 28 study days. This outcome uses the last-off approach to calculate the number of respiratory support days. The number of support days after calculated from the last day the participant was on respiratory support.
Time frame: up to 28 days
Population: All participants enrolled, eligible, and evaluable (not replaced) and included in this primary analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure | 12.1 days | Standard Deviation 11.1 |
| Placebo | Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure | 14.6 days | Standard Deviation 10.5 |
Comparison: The null hypothesis is that there is no significant difference in the number of respiratory support free days between the active drug arm and the placebo drug arm based on the student's t-test.p-value: 0.098t-test, 2 sided
Secondary
To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups.
During the first 28 days, this endpoint summarizes the number of participants who experienced adverse events (AEs) of severity grade ≥3 and whether any serious adverse events (SAEs) occurred in each study arm.
Time frame: up to 28 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Ganciclovir | To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups. | Participants with at least one reportable AE of grade 3 or greater | 13 Participants |
| IV Ganciclovir | To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups. | Participants with at least one SAE | 0 Participants |
| Placebo | To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups. | Participants with at least one reportable AE of grade 3 or greater | 11 Participants |
| Placebo | To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups. | Participants with at least one SAE | 0 Participants |
Secondary
To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure
During the first 28 study days, the number of days the participants are not on any respiratory-support is compared between the two treatment arms. Instead of using last-off approach, we will count all the days during 28 days period.
Time frame: up to 28 days
Population: All participants enrolled, eligible, and evaluable (not replaced) and included in this primary analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure | 12.9 days | Standard Deviation 11.1 |
| Placebo | To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure | 15.2 days | Standard Deviation 10.2 |
Comparison: The null hypothesis is that there is no significant difference in the number of respiratory support free days between the active drug arm and the placebo drug arm based on the student's t-test.p-value: 0.13t-test, 2 sided
Secondary
To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure.
During the first 28 study days, the number of days the participants are not on mechanical ventilation using the last off approach is compared between the two treatment arms.
Time frame: up to 28 study days
Population: Only the participants on mechanical ventilation at study entry are included. Participants on other types of respiratory support are excluded from this endpoint analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure. | 11.7 days not on mechanical ventilation | Standard Deviation 11.1 |
| Placebo | To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure. | 15.3 days not on mechanical ventilation | Standard Deviation 10.6 |
p-value: 0.04t-test, 2 sided
Secondary
To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
CMV DNA detection in plasma and endotracheal aspirate (ETA) by day 28 is defined as positive CMV PCR result from any ETA, plasma, or serum specimen collected through day 28. CMV reactivation by day 28 will be summarized with number of participants with CMV reactivation in two levels: as any detectable CMV DNA (any level) and as high-level reactivation (\>1000 IU/mL) for CMV negative patients at baseline.
Time frame: up to 28 days
Population: Participants who tested CMV negative at baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Any CMV reactivation | 5 Participants |
| IV Ganciclovir | To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | > 1000 UI/mL | 1 Participants |
| Placebo | To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Any CMV reactivation | 20 Participants |
| Placebo | To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | > 1000 UI/mL | 0 Participants |
p-value: <0.001Fine-Gray competing risks regression
p-value: 0.3Fine-Gray competing risks regression
Secondary
To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
This endpoint summarizes the days of mechanical ventilation for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded.
Time frame: up to 28 days
Population: Only the participants on mechanical ventilation at study entry are included. Participants on other types of respiratory support are excluded from this endpoint analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 10.0 days on mechanical ventilation | Standard Deviation 8.7 |
| Placebo | To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 10.4 days on mechanical ventilation | Standard Deviation 9.3 |
p-value: 0.83t-test, 2 sided
Secondary
To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
This endpoint summarizes the days of all types of respiratory support for those participants who survive the first 28 days of the study. Participants who die in the first 28 days are excluded.
Time frame: up to 28 days
Population: Participants who survive the first 28 days of this study are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 10.1 days on respiratory support | Standard Deviation 8.8 |
| Placebo | To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 11.2 days on respiratory support | Standard Deviation 9.3 |
p-value: 0.457t-test, 2 sided
Secondary
To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients.
During the first 28 study days, the number of days the participants are not in ICU using the last off approach is compared between the two treatment arms.
Time frame: up to 28 days
Population: All participants enrolled, eligible, and evaluable (not replaced) and included in this primary analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 10.9 days | Standard Deviation 10.4 |
| Placebo | To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients. | 13.9 days | Standard Deviation 9.7 |
Comparison: The null hypothesis is that there is no significant difference in the number of ICU free days between the active drug arm and the placebo drug arm based on the student's t-test.p-value: 0.037t-test, 2 sided
Secondary
To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.
This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at the end of the study (day 180).
Time frame: at the final study visit (day 180)
Population: Includes all participant enrolled, eligible, and evaluable (not replaced).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Ganciclovir | To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | 45 Participants |
| Placebo | To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | 22 Participants |
Comparison: the null hypothesis is that there is no difference between the two arms. The placebo group is the comparator group.p-value: 0.00295% CI: [1.32, 3.68]Regression, Cox
Secondary
To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.
This is a time to event outcome with death as the event and censoring at the time of study termination if the participant is alive at 28 days. The hazard ratio and Cox proportional hazards models are used for this endpoint.
Time frame: at study day 28
Population: Includes all participant enrolled, eligible, and evaluable (not replaced).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Ganciclovir | To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | 34 Participants |
| Placebo | To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively. | 13 Participants |
Comparison: The null hypothesis is that there is no difference between the two arms. The placebo arm is the comparison group.p-value: 0.00395% CI: [1.4, 5.02]Regression, Cox
Secondary
To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients.
The PaO2/FiO2 (P/F) ratio was used to define oxygenation. The P/F ratio was summarized over the first 7 days of the study. The lowest PaO2 value within each study day was reported and used in the oxygenation calculation. If the PaO2 value was not available, an estimate of PaO2 was calculated from the SpO2 lowest value.
Time frame: up to 7 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 3 | 178.9 PaO2/FiO2 | Standard Deviation 72 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 5 | 184.6 PaO2/FiO2 | Standard Deviation 80.3 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 2 | 177.3 PaO2/FiO2 | Standard Deviation 78.3 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 6 | 209.1 PaO2/FiO2 | Standard Deviation 80.8 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 4 | 190.5 PaO2/FiO2 | Standard Deviation 87.8 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 7 | 193.5 PaO2/FiO2 | Standard Deviation 81.1 |
| IV Ganciclovir | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 1 | 155.4 PaO2/FiO2 | Standard Deviation 78.4 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 7 | 198.5 PaO2/FiO2 | Standard Deviation 88.2 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 1 | 184.8 PaO2/FiO2 | Standard Deviation 132.9 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 2 | 186.8 PaO2/FiO2 | Standard Deviation 112.2 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 3 | 186.8 PaO2/FiO2 | Standard Deviation 106.5 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 4 | 189.4 PaO2/FiO2 | Standard Deviation 79.1 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 5 | 196.3 PaO2/FiO2 | Standard Deviation 80.5 |
| Placebo | To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients. | Oxygenation Day 6 | 199.1 PaO2/FiO2 | Standard Deviation 106.6 |