Randomized Trial to Evaluate Suppressive Effect of High-Dose Acyclovir Versus Once-Daily Valacyclovir on Persons With HSV-2

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00362297
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of the research study is to evaluate the effectiveness of high-dose acyclovir compared to valacyclovir for reduction of asymptomatic genital shedding in persons with genital herpes.

The study will enroll men and women who are 18 years or older, test positive to HSV-2 (by blood test) and have had a first outbreak of HSV-2 within the past 6 months or have had at least 4 genital herpes outbreaks in the past year. Participants must be HIV negative and willing to stop taking suppressive therapy for HSV for the one week wash out period. (Females only: You must not be pregnant or breast-feeding). Both men and women will be asked to use an effective form of birth control.

Involvement in the study will last 15-weeks and you will be asked to visit the clinic every 2-weeks. At each visit, you will be given medication to take daily (either valacyclovir or acyclovir; you will receive both medications at some point during this study). There will be a total of 9 study visits and each visit will last approximately 30 minutes. We will ask that you complete a daily symptom diary and collected daily home swabs 4-times a day, everyday during the study. Each daily home swab will take less than 3 minutes to perform.

Condition or Disease	Intervention/Treatment	Phase
Genital Herpes	Drug: acyclovir; Drug: valacyclovir	Phase 4

Detailed Description

Screening Assessment

Patients will be assessed for their eligibility to enter the study at a screening visit. After signing informed consent they will undergo a medical history and the following information will be recorded in the Case Report Form (CRF):

• Demographic Data: Date of birth, sex, marital status, education and race

• Previous antiviral medication taken

• History of sexually transmitted infections and sexual history.

Start of Study Visit (Day 0) and Day 14, 28, 42, 56, 70, 84, 98 and 105 Follow-Up Visits.

Eligible patients will return to clinic to be given study drug and a patient diary card on which to record concomitant medications, signs and symptoms, and adverse experiences. The investigator will instruct the patient on daily home viral sample collection, taking the study drug, and completing the diary card. The patient will be instructed to return to clinic in 2 weeks, +/- 2 days. Medication compliance will be assessed at each visit using pill counts.

Crossover Study Visit Prior To Washout Period (Day 49-55)

Participants will not be given study drug or placebo during the 7-day washout period.

Daily Home Viral Sample Collection

Participants will collect swabs from the genital mucosa four times per day and store the samples in PCR media with preprinted labels. Women will swab the cervicovaginal, vulvar and perianal areas, and men will swab the penile and perianal. Every two weeks, they will return the samples to the Virology Research Clinic when they present for additional study drug and assessment.

Final Study Visit (Day 105)

At the final study visit at Day 105 or for premature discontinuation, the investigator will perform the activities at the regular study visits, with the exception of the dispensation of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Cross-Over Study to Evaluate the Suppressive Effect of High-Dose Acyclovir Versus Once Daily Valacyclovir on Herpes Simplex Virus Type 2 Genital Shedding in Herpes Simplex Virus-2 Seropositive Adults
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard dose	Drug: valacyclovir; 500 mg orally once daily for 7 weeks; Other Names: Valtrex
Experimental: High-dose	Drug: acyclovir; 800 mg orally three times daily for 7 weeks

Outcome Measures

Primary Outcome Measures

1. Frequency of HSV-2 Total Shedding From the Genital Tract as Measured by PCR, Calculated Using a Per-day Shedding Rate in Participants Treated With High-dose Acyclovir as Compared to Once-daily Valacyclovir. [15 weeks]

   Participants were treated with both interventions in a cross-over study design. Shedding rates on each drug arm per participant were compared by Poisson regression. Shedding rates were calculated by dividing the number of positive swabs by the total number of swabs for each intervention group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years or older;

2. HSV-2 seropositive by Western Blot;

3. not receiving any drugs with known anti-HSV-2 activity for study duration;

4. history of primary genital herpes infection within past 6 months OR history of 4 or more HSV recurrences per year during the past year OR 4 or more recurrences per year prior to initiation of suppressive antiviral therapy;

5. able to comply with the study protocol;

6. women of child bearing potential who are sexually active with men must be using a medically accepted method of contraception as judged by the investigator;

7. women of child-bearing potential must have a negative pregnancy test (urine) at screening visit;

8. in general good health, without other serious medical conditions and specifically with normal renal and hepatic function, as determined by the patient's medical history;

9. planning to remain resident in the area of the study center for the duration of the study participation;

10. HIV seronegative.

Exclusion Criteria:

1. hypersensitivity to acyclovir or valacyclovir;

2. pregnant women;

3. HIV positive or other immunosuppressed state, including chronic steroid use. Intermittent nasal or topical steroids are acceptable

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Washington Virology Research Clinic	Seattle	Washington	United States	98104

Sponsors and Collaborators

• University of Washington

Investigators

• Principal Investigator: Christine Johnston, MD, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Christine Johnston, Acting Assistant Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT00362297
• Other Study ID Numbers: 30520-D - Phase 1
• First Posted: Aug 9, 2006
• Last Update Posted: Nov 18, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Herpes Genitalis; Valacyclovir; Acyclovir

Study Results

Participant Flow

Recruitment Details	Dates of recruitment: November 2006-August 2008 Site: University of Washington Virology Research Clinic, Seattle, WA

Arm/Group Title	Standard Dose First, Then High Dose	High Dose First, Then Standard Dose
Arm/Group Description
Period Title: Treatment 1 (Initial Drug Assignment)
STARTED	16	15
COMPLETED	16	11
NOT COMPLETED	0	4
Period Title: Treatment 1 (Initial Drug Assignment)
STARTED	16	11
COMPLETED	16	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard Dose	High-dose	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	16	15	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.6 (13.2)	39.1 (12.2)	40.5 (12.6)
Sex: Female, Male (Count of Participants)
Female	10 62.5%	9 60%	19 61.3%
Male	6 37.5%	6 40%	12 38.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 6.7%	1 3.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.3%	2 13.3%	3 9.7%
White	13 81.3%	10 66.7%	23 74.2%
More than one race	2 12.5%	0 0%	2 6.5%
Unknown or Not Reported	0 0%	2 13.3%	2 6.5%

Outcome Measures

1. Primary Outcome

Title	Frequency of HSV-2 Total Shedding From the Genital Tract as Measured by PCR, Calculated Using a Per-day Shedding Rate in Participants Treated With High-dose Acyclovir as Compared to Once-daily Valacyclovir.
Description	Participants were treated with both interventions in a cross-over study design. Shedding rates on each drug arm per participant were compared by Poisson regression. Shedding rates were calculated by dividing the number of positive swabs by the total number of swabs for each intervention group.
Time Frame	15 weeks

Outcome Measure Data

Analysis Population Description

Participants who did not collect at least one swab on each arm of the cross-over were excluded from analysis.

Arm/Group Title	Standard Dose Valacyclovir	High Dose Acyclovir
Arm/Group Description
Measure Participants	27	27
Measure Swabs	4663	4709
Number [percentage of swabs with HSV detected]	4	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Dose Valacyclovir
	Comments	Comparison of genital HSV shedding rate on high dose acyclovir to standard dose valacyclovir. Powered with 80% chance of detecting 50% reduction in genital shedding rate on high dose acyclovir compared to standard dose valacyclovir.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments
	Method	Regression, Poisson
	Comments	Adjusted for period effects.
Method of Estimation	Estimation Parameter	Incident Risk Ratio
	Estimated Value	0.79
	Confidence Interval	() 95%; 0.63 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Standard Dose		High-dose
Arm/Group Description
All Cause Mortality
	Standard Dose		High-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Dose		High-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Standard Dose		High-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/31 (0%)

Limitations/Caveats

The trial was performed at a single site, and enrolled mostly white, healthy, sexually active adults with high rates of genital HSV-2 recurrence. The results may not be generalizable to other populations.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.