Trial Outcomes & Findings for Acyclovir for Herpes Infections Involving the Central Nervous System in Neonates (NCT NCT00031460)

Last Updated: 2012-05-16

Results Overview

Motor scores of all participants completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: greater than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development; and less than or equal to 69 suggests significant delayed development.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

46 participants

Primary outcome timeframe

At 12 months of life.

Results posted on

2012-05-16

Participant Flow

Neonates diagnosed with HSV-1 or HSV-2 \<= 28 days of age with evidence of CNS HSV disease (with or without evidence of viral dissemination to other organs, such as the skin, liver, and lungs) then treated with intravenous acyclovir therapy. Subject has negative CSF PCR results within 48 hours prior to completion of intravenous acyclovir therapy.

Subjects enrolled while on 2 - 3 weeks of IV acyclovir therapy who have positive cerebrospinal Fluid (CSF) herpes simplex virus (HSV) PCR results within 48 hours prior to IV therapy completion, are not randomized.

Participant milestones

Participant milestones
Measure	Acyclovir Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo Identical volume as acyclovir.
Overall Study STARTED	24	22
Overall Study COMPLETED	15	8
Overall Study NOT COMPLETED	9	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Acyclovir Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo Identical volume as acyclovir.
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	1	1
Overall Study Non-Compliant	1	1
Overall Study Death	0	1
Overall Study Reactivation of Disease	5	9
Overall Study Disruption of blinded drug supply	2	0
Overall Study Confirmed unevaluable	0	1

Baseline Characteristics

Acyclovir for Herpes Infections Involving the Central Nervous System in Neonates

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acyclovir n=24 Participants Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=22 Participants Identical volume as acyclovir.	Total n=46 Participants Total of all reporting groups
Age, Customized	11 days FULL_RANGE 1.71 • n=5 Participants	15.5 days FULL_RANGE 1.42 • n=7 Participants	13 days FULL_RANGE 1.13 • n=5 Participants
Age, Customized <=28 days	24 participants n=5 Participants	22 participants n=7 Participants	46 participants n=5 Participants
Age, Customized Between 18 and 65 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized >=65 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	22 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: At 12 months of life.

Outcome measures

Outcome measures
Measure	Acyclovir n=15 Participants Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=8 Participants Identical volume as acyclovir.
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). Units: participants	10 participants	5 participants
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). Number of participants with score > or = 115	0 participants	1 participants
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). Number of participants with score 85 - 114	6 participants	2 participants
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). Number of participants with score 70 - 84	0 participants	0 participants
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). Number of participants with score< or = 69	4 participants	2 participants

PRIMARY outcome

Timeframe: At 12 months of life.

Mental scores of all subjects completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: greater than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development; and less than or equal to 69 suggests significant delayed development.

Outcome measures

Outcome measures
Measure	Acyclovir n=15 Participants Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=8 Participants Identical volume as acyclovir.
Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) Participants with score 70 - 84	0 participants	0 participants
Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) Number of participants reporting scores	10 participants	6 participants
Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) Participants with score > or = 115	0 participants	1 participants
Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) Participants with score 85 - 114	7 participants	1 participants
Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) Participants with score < or = 69	3 participants	4 participants

SECONDARY outcome

Timeframe: post randomization - 12 months

Number of participants experiencing 2 or fewer HSV recurrences during the first 12 months of life as measured by assessments and reports at study visits.

Outcome measures

Outcome measures
Measure	Acyclovir n=15 Participants Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=8 Participants Identical volume as acyclovir.
Number of Participants With Two or Fewer Episodes of Cutaneous Recurrence of Herpes Simplex Virus (HSV) Disease Post-randomization During the Initial 12 Months of Life. Number of participants reporting recurrences	6 participants	3 participants
Number of Participants With Two or Fewer Episodes of Cutaneous Recurrence of Herpes Simplex Virus (HSV) Disease Post-randomization During the Initial 12 Months of Life. Participants with < or = 2 recurrences	3 participants	1 participants
Number of Participants With Two or Fewer Episodes of Cutaneous Recurrence of Herpes Simplex Virus (HSV) Disease Post-randomization During the Initial 12 Months of Life. Participants with > 2 recurrences	3 participants	2 participants

SECONDARY outcome

Timeframe: post randomization - 12 months

Number of participants assessed to have a positive herpes simplex virus (HSV) DNA by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) at any time during their initial 12 months of life after treatment. The PCR is a technique to help visualize copies of a piece of DNA.

Outcome measures

Outcome measures
Measure	Acyclovir n=15 Participants Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=8 Participants Identical volume as acyclovir.
Detection of Herpes Simplex Virus (HSV) DNA in the Cerebrospinal Fluid (CSF) by PCR at Anytime During the Initial 12 Months of Life. Number of participants reporting = or >1 + CSF PCR	12 participants	6 participants
Detection of Herpes Simplex Virus (HSV) DNA in the Cerebrospinal Fluid (CSF) by PCR at Anytime During the Initial 12 Months of Life. Number of participants reporting 0 - CSF PCR	3 participants	2 participants

Adverse Events

Acyclovir

Serious events: 17 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 15 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Acyclovir n=24 participants at risk Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=21 participants at risk Identical volume as acyclovir.
Blood and lymphatic system disorders Neutropenia	45.8% 11/24 • Number of events 17 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	19.0% 4/21 • Number of events 4 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Herpes simplex virus	25.0% 6/24 • Number of events 21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	38.1% 8/21 • Number of events 26 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Otitis media	29.2% 7/24 • Number of events 10 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	38.1% 8/21 • Number of events 12 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Upper respiratory infection	29.2% 7/24 • Number of events 12 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	28.6% 6/21 • Number of events 10 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.

Additional Information

Penelope M. Jester

Collaborative Antiviral Study Group

Phone: (205) 934-2424

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Acyclovir n=24 participants at risk Oral suspension 300 mg/m\^2/dose TID for 6 months.	Placebo n=21 participants at risk Identical volume as acyclovir.
Blood and lymphatic system disorders Decreased neutrophils	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Blood and lymphatic system disorders Neutropenia	37.5% 9/24 • Number of events 9 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	19.0% 4/21 • Number of events 4 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Cardiac disorders Bradycardia	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Gastrointestinal disorders Dehydration	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Gastrointestinal disorders Feeding dysfunction	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Gastrointestinal disorders Gastroenteritis	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Gastrointestinal disorders Gastroesophageal reflux	8.3% 2/24 • Number of events 2 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Herpes simplex virus	16.7% 4/24 • Number of events 5 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	38.1% 8/21 • Number of events 13 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Otitis media	8.3% 2/24 • Number of events 2 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Rotavirus	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Tuberculosis	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Nervous system disorders Hydrocephalus	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Nervous system disorders Seizures	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	14.3% 3/21 • Number of events 3 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Respiratory, thoracic and mediastinal disorders Apnea	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia	4.2% 1/24 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Eye disorders Strabismus	0.00% 0/24 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	0.00% 0/21 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
General disorders Fever	0.00% 0/24 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Infections and infestations Infantile spasms	0.00% 0/24 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.
Skin and subcutaneous tissue disorders Abscess	0.00% 0/24 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.	4.8% 1/21 • Number of events 1 • Adverse events were followed throughout the 5 years of the study subject participation, or until subject terminated from the study. Subjects not completing 6 months of study drug were followed as intent to treat. Twenty-two participants were enrolled into the placebo arm; however, only 21 received study drug.