Trial Outcomes & Findings for Ganciclovir/Valganciclovir for Prevention of CMV Reactivation in Acute Injury of the Lung and Respiratory Failure (NCT NCT01335932)

Results Overview

Change between baseline and 14 days post-randomization between placebo \& ganciclovir groups

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

160 participants

Primary outcome timeframe

Baseline and Day 14

Results posted on

2018-08-21

Participant Flow

Participant milestones

Participant milestones
Measure	IV Ganciclovir 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Overall Study STARTED	84	76
Overall Study COMPLETED	84	72
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ganciclovir/Valganciclovir for Prevention of CMV Reactivation in Acute Injury of the Lung and Respiratory Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=76 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.	Total n=160 Participants Total of all reporting groups
Age, Continuous	55.2 years n=5 Participants	58.2 years n=7 Participants	56.6 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	40 Participants n=7 Participants	89 Participants n=5 Participants
Region of Enrollment United States	84 participants n=5 Participants	76 participants n=7 Participants	160 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 14

Change between baseline and 14 days post-randomization between placebo \& ganciclovir groups

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Serum IL-6 Level	-0.79 pg/mL Standard Deviation 0.65	-0.79 pg/mL Standard Deviation 0.69

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of participants in baseline negatives with CMV reactivation at any level at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=77 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=67 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Participants With CMV Reactivation at 28 Days in Plasma CMV viremia at any level	3 Participants	23 Participants
Number of Participants With CMV Reactivation at 28 Days in Plasma no CMV viremia at any level	74 Participants	44 Participants

SECONDARY outcome

Timeframe: at 7 days post-randomization

Population: The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Levels of IL-6 from BALs at 7 days post-randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=3 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=7 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
BAL Levels of IL-6	1.01 log 10 pg/mL Standard Deviation 0.78	1.66 log 10 pg/mL Standard Deviation 1.26

SECONDARY outcome

Timeframe: at 14 days post-randomization

Number of participants experiencing organ system failure at 14 days

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Participants With Organ System Failure at 14 Days with organ failure	0 Participants	2 Participants
Number of Participants With Organ System Failure at 14 Days without organ failure	84 Participants	70 Participants

SECONDARY outcome

Timeframe: by 28 days post-randomization

Number of ICU days alive and not in the ICU by day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Days Alive and Not in the ICU	10.02 days Standard Deviation 6.84	10.97 days Standard Deviation 8.23

SECONDARY outcome

Timeframe: by 180 days post-randomization

Need to be biopsy-proven

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
CMV Disease Biopsy proven CMV disease	0 Participants	0 Participants
CMV Disease No Biopsy proven CMV disease	84 Participants	72 Participants

SECONDARY outcome

Timeframe: by 35 days post-randomization

Number of patients with greater than one AE of grade 3 or more

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Grade 3 AEs or Higher number without AE greater than grade 3	73 Participants	62 Participants
Grade 3 AEs or Higher number with AE greater than grade 3	11 Participants	10 Participants

SECONDARY outcome

Timeframe: at 1 day post-randomization

Physical Component Summary of SF-36. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=53 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=35 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
SF-36 Health Survey	36.37 scores on a scale Standard Deviation 10.93	35 scores on a scale Standard Deviation 11.28

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of participants with CMV reactivation \>1,000 IU per mL at day 28 in plasma

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=77 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=67 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Incidence of CMV Reactivation >1,000 IU Per mL at Day 28 in Plasma CMV viremia >1,000 copies per mL	0 Participants	5 Participants
Incidence of CMV Reactivation >1,000 IU Per mL at Day 28 in Plasma No CMV viremia >1,000 copies per mL	77 Participants	62 Participants

SECONDARY outcome

Timeframe: at 28 days post-randomization

CMV reactivation in baseline negatives at any level at day 28 in throat

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=80 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=67 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Incidence of CMV Reactivation at Any Level at 28 Days in Throat CMV reactivation at any level at day 28 in throat	2 Participants	6 Participants
Incidence of CMV Reactivation at Any Level at 28 Days in Throat No CMV reactivation at any level at day 28in throa	78 Participants	61 Participants

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of participants with CMV reactivation \>1,000 IU per mL at day 28 in throat

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=80 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=67 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Incidence of CMV Reactivation >1,000 IU Per mL at 28 Days in Throat CMV reactivation >1,000 in IU per mL	0 Participants	1 Participants
Incidence of CMV Reactivation >1,000 IU Per mL at 28 Days in Throat No CMV reactivation >1,000 IU per mL in throat	80 Participants	66 Participants

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

CMV AUC in blood from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
CMV AUC in Blood	0.11 IU*day/mL Standard Deviation 0.39	0.39 IU*day/mL Standard Deviation 0.69

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

CMV AUC in Throat from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
CMV AUC in Throat	0.03 IU*day/mL Standard Deviation 0.14	0.17 IU*day/mL Standard Deviation 0.52

SECONDARY outcome

Timeframe: at 28 days post-randomization

CMV Peak Viremia in blood at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
CMV Peak Viral Load in Blood	0.24 log 10 IU/mL Standard Deviation 0.67	0.89 log 10 IU/mL Standard Deviation 1.21

SECONDARY outcome

Timeframe: at 7 days post-randomization

Population: The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Levels of IL-8 in BALs at day 7

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=3 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=7 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
BAL Levels of IL-8	2.21 log 10 pg/mL Standard Deviation 0.66	2.61 log 10 pg/mL Standard Deviation 1.22

SECONDARY outcome

Timeframe: at 7 days post-randomization

Population: The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Levels of TNFa in BALs at day 7

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=3 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=7 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
BAL Levels of TNFa	0.18 log 10 pg/mL Standard Deviation 0	0.46 log 10 pg/mL Standard Deviation 0.49

SECONDARY outcome

Timeframe: at 7 days post-randomization

Plasma levels of IL-6.

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=75 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=57 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of IL-6	0.87 log 10 pg/mL Standard Deviation 0.84	0.92 log 10 pg/mL Standard Deviation 0.62

SECONDARY outcome

Timeframe: at 7 days post-randomization

Levels of IL-8 in plasma at day 7

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=75 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=57 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of IL-8	1.38 log 10 pg/mL Standard Deviation 0.6	1.38 log 10 pg/mL Standard Deviation 0.35

SECONDARY outcome

Timeframe: at 7 days post-randomization

Plasma levels of TNF a at day 7.Cytokines are summarized on log 10 scale. When logged value is negative, the raw value would be less than 1.

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=75 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=57 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of TNF a	-0.07 log 10 pg/mL Standard Deviation 0.36	-0.1 log 10 pg/mL Standard Deviation 0.35

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

Population: Cytokines are summarized on a log 10 scale. When the logged value is negative, the raw value would be less than 1.

Plasma levels of TNF a from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=33 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=31 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of TNF a	-0.06 log 10 pg/mL Standard Deviation 0.37	-0.11 log 10 pg/mL Standard Deviation 0.27

SECONDARY outcome

Timeframe: at 28 days post-randomization

Plasma levels of IL-6 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=33 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=31 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of IL-6	0.35 log 10 pg/mL Standard Deviation 0.51	0.59 log 10 pg/mL Standard Deviation 0.7

SECONDARY outcome

Timeframe: at 28 days post-randomization

Plasma levels of IL-8 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=33 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=31 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of IL-8	1.09 log 10 pg/mL Standard Deviation 0.46	1.27 log 10 pg/mL Standard Deviation 0.46

SECONDARY outcome

Timeframe: at 28 days post-randomization

Plasma levels of soluble ICAM-1 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=33 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=31 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of Soluble ICAM-1	5.34 log 10 pg/mL Standard Deviation 0.19	5.48 log 10 pg/mL Standard Deviation 0.22

SECONDARY outcome

Timeframe: at 7 days post-randomization

Plasma levels of soluble ICAM-1 at day 7

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=75 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=57 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Plasma Levels of Soluble ICAM-1	5.43 log 10 pg/mL Standard Deviation 0.21	5.45 log 10 pg/mL Standard Deviation 0.31

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

Peak Plasma levels of soluble ICAM-1 from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Peak Plasma Levels of Soluble ICAM-1	5.52 log 10 pg/mL Standard Deviation 0.2	5.57 log 10 pg/mL Standard Deviation 0.27

SECONDARY outcome

Timeframe: at 28 days post-randomization

Peak Plasma levels of TNF-a at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Peak Plasma Levels of TNF-a	0.16 log 10 pg/mL Standard Deviation 0.3	0.17 log 10 pg/mL Standard Deviation 0.36

SECONDARY outcome

Timeframe: at 28 days post-randomization

Peak Plasma levels of IL-10 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Peak Plasma Levels of IL-10	0.88 log 10 pg/mL Standard Deviation 0.52	0.82 log 10 pg/mL Standard Deviation 0.49

SECONDARY outcome

Timeframe: at 28 days post-randomization

Peak Plasma levels of IL-8 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Peak Plasma Levels of IL-8	1.67 log 10 pg/mL Standard Deviation 0.65	1.66 log 10 pg/mL Standard Deviation 0.44

SECONDARY outcome

Timeframe: at 28 days post-randomization

Peak Plasma levels of IL-6 at day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Peak Plasma Levels of IL-6	1.57 log 10 pg/mL Standard Deviation 0.78	1.56 log 10 pg/mL Standard Deviation 0.78

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

AUC Plasma levels of IL-6 from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
AUC Plasma Levels of IL-6	0.68 IU*day/mL Standard Deviation 0.49	0.75 IU*day/mL Standard Deviation 0.51

SECONDARY outcome

Timeframe: Day 0 to 28 days post-randomization

AUC Plasma levels of IL-8 from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
AUC Plasma Levels of IL-8	1.15 IU*day/mL Standard Deviation 0.45	1.13 IU*day/mL Standard Deviation 0.42

SECONDARY outcome

Timeframe: at 28 days post-randomization

AUC Plasma levels of IL-10 from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
AUC Plasma Levels of IL-10	0.36 IU*day/mL Standard Deviation 0.36	0.35 IU*day/mL Standard Deviation 0.38

SECONDARY outcome

Timeframe: at 28 days post-randomization

AUC Plasma levels of TNF-a from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
AUC Plasma Levels of TNF-a	-0.14 IU*day/mL Standard Deviation 0.28	-0.14 IU*day/mL Standard Deviation 0.25

SECONDARY outcome

Timeframe: at 28 days post-randomization

AUC Plasma levels of soluble ICAM-1 from day 0 to day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
AUC Plasma Levels of Soluble ICAM-1	4.78 IU*day/mL Standard Deviation 0.98	4.65 IU*day/mL Standard Deviation 1.25

SECONDARY outcome

Timeframe: by 180 days post-randomization

Hospital days alive and not hospitalized by day 180

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=55 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=47 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Length of Stay	145.13 days Standard Deviation 47.63	145.94 days Standard Deviation 47.88

SECONDARY outcome

Timeframe: by 28 days post-randomization

Hospital days alive and not hospitalized by day 28

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=78 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=69 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Length of Stay	9.96 days Standard Deviation 8.52	8.72 days Standard Deviation 8.24

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of participants with organ system failure at 28 days

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Organ System Failure at 28 Days with organ failure	0 Participants	2 Participants
Organ System Failure at 28 Days without organ failure	84 Participants	70 Participants

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of days of mechanical ventilation duration as assessed by ventilator free days

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Duration of Mechanical Ventilation as Assessed by Ventilator Free Days	18.71 days Standard Deviation 9.08	15.97 days Standard Deviation 9.72

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of days of mechanical ventilation duration as assessed by ventilator days

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Duration of Mechanical Ventilation as Assessed by Ventilator Days	6.95 days Standard Deviation 6.16	8.5 days Standard Deviation 7.17

SECONDARY outcome

Timeframe: at 28 days post-randomization

Number of participants with bacteremia and/or fungemia

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Bacteremia and/or Fungemia with bacteremia and /or fungemia	15 Participants	11 Participants
Bacteremia and/or Fungemia without bacteremia and /or fungemia	69 Participants	61 Participants

SECONDARY outcome

Timeframe: at 60 days post-randomization

Mortality at 60 days post randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Mortality dead	13 Participants	12 Participants
Mortality alive	71 Participants	60 Participants

SECONDARY outcome

Timeframe: at 180 days post-randomization

Mortality at 180 days post-randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Mortality at 180 Days alive	66 Participants	53 Participants
Mortality at 180 Days dead	18 Participants	19 Participants

SECONDARY outcome

Timeframe: at 180 days post-randomization

Physical Component Summary at 180 days post- randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=40 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=34 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
SF-36 Functional Assessment Physical Component	35.51 scores on a scale Standard Deviation 11.38	38.17 scores on a scale Standard Deviation 10.96

SECONDARY outcome

Timeframe: at 180 days post-randomization

Mental Component Summary at 180 days post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=40 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=34 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
SF-36 Functional Assessment Mental Component	45.55 scores on a scale Standard Deviation 11.52	44.08 scores on a scale Standard Deviation 12.25

SECONDARY outcome

Timeframe: at 1 day post-randomization

SF-36 Mental Component Summary at 1 day post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=53 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=35 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
SF-36 Functional Assessment Mental Component on Day 1	43.83 scores on a scale Standard Deviation 12	42.73 scores on a scale Standard Deviation 13.78

SECONDARY outcome

Timeframe: by 35 days post-randomization

Number of patients with Serious Adverse Events by day 35

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Patients With Serious Adverse Events Number of patients with a Serious adverse event	0 Participants	0 Participants
Patients With Serious Adverse Events Number of patients without a Serious adverse event	84 Participants	72 Participants

SECONDARY outcome

Timeframe: by 35 days post-randomization

Time to neutropenia by 35 days post-randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Time to Neutropenia	0 days	0 days

SECONDARY outcome

Timeframe: by 35 days post-randomization

Number of participants requiring Granulocyte-colony stimulating factor

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Use of Granulocyte-colony Stimulating Factor Number of patients that required GCSF	0 Participants	0 Participants
Use of Granulocyte-colony Stimulating Factor Number of patients that did not require GCSF	84 Participants	72 Participants

SECONDARY outcome

Timeframe: by 35 days post-randomization

Number of patients experiencing a glomerular filtration rate \< 60mL/min at day 35

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Renal Insufficiency Glomerular filtration rate less than 60 mL/min	36 Participants	41 Participants
Renal Insufficiency Glomerular filtration rate greater than 60 mL/min	48 Participants	31 Participants

SECONDARY outcome

Timeframe: by 35 days post-randomization

Red blood cell transfusions required per patients by day 35

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Red Blood Cell Transfusions Required Per Patients	2 transfusions Interval 1.0 to 2.0	1 transfusions Interval 1.0 to 4.0

SECONDARY outcome

Timeframe: by 35 days post-randomization

Platelet transfusions per patient

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=721 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Platelet Transfusions	1 transfusions Interval 1.0 to 1.0	1 transfusions Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: at 14 days post-randomization

Composite of survival status and \>7 days ventilation status, and IL-6 levels. In the composite analysis, the endpoint is composed by death, ventilation status and change of cytokine.

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=84 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=72 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Clinical Outcomes Number of patients with composite endpoint	42 Participants	49 Participants
Clinical Outcomes Number of patients without composite endpoint	42 Participants	23 Participants

SECONDARY outcome

Timeframe: at 7 days post-randomization

Bacteremia and fungemia outcomes among subjects who survive at least 7 days

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Bacteremia and Fungemia Outcomes number of events	15 events	9 events
Bacteremia and Fungemia Outcomes number of no events	67 events	55 events

SECONDARY outcome

Timeframe: at 7 through 14 days post-randomization

Bacteremia and fungemia events among subjects who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Bacteremia and Fungemia Outcomes in Mechanically Ventilated Subjets number of events	6 events	9 events
Bacteremia and Fungemia Outcomes in Mechanically Ventilated Subjets number of no events	24 events	24 events

SECONDARY outcome

Timeframe: at 7 days post-randomization

Overall mortality amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Overall Mortality number of deaths	16 events	11 events
Overall Mortality number of alive	66 events	53 events

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of mechanical ventilated days amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Mechanical Ventilated Days	7.05 days Standard Deviation 6.19	9.05 days Standard Deviation 7.4

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of ventilator-free days amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Ventilator-free Days	19.17 days Standard Deviation 8.7	17.97 days Standard Deviation 8.37

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of days in the ICU amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Days in the ICU	10.20 days Standard Deviation 6.82	11.83 days Standard Deviation 8.32

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of ICU-free days amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=82 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=64 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of ICU-free Days	15.38 days Standard Deviation 27	13.89 days Standard Deviation 25

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of days in the hospital amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=67 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=57 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Days in the Hospital	6.21 days Standard Deviation 4.85	5.53 days Standard Deviation 4.9

SECONDARY outcome

Timeframe: at 7 days post-randomization

Number of hospital-free days amongst subjects who survive at least 7 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=76 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=61 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Hospital-free Days	10.22 days Standard Deviation 8.47	9.87 days Standard Deviation 8.09

SECONDARY outcome

Timeframe: 28 days

Mortality among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Mortality Among Subjects Mechanically Ventilated From Day 7 to 14 number of events	9 events	6 events
Mortality Among Subjects Mechanically Ventilated From Day 7 to 14 number of no events	21 events	27 events

SECONDARY outcome

Timeframe: 28 days

Number of mechanically ventilated days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Mechanically Ventilated Days Among Subjects by Day 28	13.4 days Standard Deviation 6.12	14.42 days Standard Deviation 6.64

SECONDARY outcome

Timeframe: 28 days

Number of ventilator-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Ventilator-free Days Among Subjects by Day 28	11.4 days Standard Deviation 8.29	12.45 days Standard Deviation 7.26

SECONDARY outcome

Timeframe: 28 days

Number of days in ICU amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Days in ICU Amongst Subjects by Day 28	16.73 days Standard Deviation 5.75	17.79 days Standard Deviation 7.41

SECONDARY outcome

Timeframe: 28 days

Number of ICU-free days amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=30 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=33 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of ICU-free Days Amongst Subjects by Day 28	7.73 days Standard Deviation 18	8.15 days Standard Deviation 18

SECONDARY outcome

Timeframe: 28 days

Number of hospital-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Outcome measures

Outcome measures
Measure	IV Ganciclovir n=28 Participants 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir 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.	Placebo n=32 Participants normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Number of Hospital-free Days Among Subjects by Day 28	3.54 days Standard Deviation 5.15	4.59 days Standard Deviation 5.55

Adverse Events

IV Ganciclovir

Serious events: 0 serious events

Other events: 0 other events

Deaths: 10 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 11 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr.Michael Boeckh

FHCRC

Phone: 206 667-6706

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place