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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00001038




Registration number
NCT00001038
Ethics application status
Date submitted
2/11/1999
Date registered
31/08/2001
Date last updated
1/03/2011

Titles & IDs
Public title
A Study of Valacyclovir Hydrochloride in the Prevention of Life-Threatening Cytomegalovirus Disease in HIV-Infected Patients
Scientific title
A Randomized, Double-Blind Trial of Valacyclovir Hydrochloride (BW 256U87) Prophylaxis for Opportunistic Cytomegalovirus End-Organ Disease in Patients With Advanced HIV Infection (< 100 CD4+ Lymphocytes)
Secondary ID [1] 0 0
FDA 104C
Secondary ID [2] 0 0
ACTG 204
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus Infections 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
Inclusion Criteria

Concurrent Medication:

Recommended:

* PCP prophylaxis.

Allowed:

* Any antiretroviral therapies available by prescription or through expanded access or Treatment IND programs, including combination or sequential use.
* Chemotherapy for Kaposi's sarcoma, lymphoma, or other malignancies IF patient is hematologically stable for at least 30 days prior to study entry.
* Discrete courses of oral or parenteral acyclovir for VZV or HSV infection, not to exceed 21 days per episode (may co-enroll on ACTG 169). For recurrent episodes, open-label acyclovir for a total of 60 days over a 12-month period is allowed. Study drug is interrupted.
* Supportive therapies available by prescription, expanded access, or Treatment IND programs, such as G-CSF, GM-CSF, and erythropoietin.
* Other medications necessary for the patient's welfare, at the discretion of the investigator.

Patients must have:

* HIV infection or AIDS-defining conditions.
* CD4+ count < 100 cells/mm3.
* IgG antibodies to CMV.
* No active CMV disease or history of CMV end-organ disease.
* Consent of parent or guardian if less than 18 years of age.
* Ability to comply with protocol.

NOTE:

* Patients may be co-enrolled in ACTG primary infection Phase II/III studies, ACTG opportunistic infection protocols, or treatment protocols or similar studies sponsored by other research networks as long as those studies do not violate the restrictions placed on concomitant therapies and toxicity management.

Prior Medication:

Allowed:

* PCP prophylaxis.
* Any antiretroviral therapies available by prescription or through expanded access or Treatment IND programs, including combination or sequential use.
* Chemotherapy for Kaposi's sarcoma, lymphoma, or other malignancies.
* Acyclovir.
* Supportive therapies available by prescription, expanded access, or Treatment IND programs, such as G-CSF, GM-CSF, and erythropoietin.
Minimum age
13 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

* Nausea or vomiting that precludes oral dosing.
* Ocular media opacities that preclude adequate visualization of fundi.
* Pregnancy.
* Known hypersensitivity to acyclovir.
* Known lactose intolerance.

Concurrent Medication:

Excluded:

* Systemic interferons and immunomodulators (including CMV hyperimmune serum/globulin and chronic corticosteroids at doses in excess of physiologic replacement).
* Probenecid.
* Investigational or marketed agents with potential activity against CMV, herpes simplex, and/or Varicella zoster, EXCEPT as specifically allowed.

Patients with the following prior condition are excluded:

* Pre-existing necrotizing retinopathy that may interfere with a subsequent diagnosis of CMV retinitis.

Prior Medication:

Excluded:

* Prior ganciclovir, foscarnet, or any investigational anti-CMV agent including use of foscarnet for acyclovir-resistant herpes.
* Interferons, immunomodulators (other than colony stimulating factors), or CMV hyperimmune globulin within 30 days prior to study entry.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Saint Vincent's Hosp Med Centre - Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Denmark
State/province [19] 0 0
Hvidore
Country [20] 0 0
France
State/province [20] 0 0
Paris Cedex 12
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Italy
State/province [22] 0 0
Rome
Country [23] 0 0
Sweden
State/province [23] 0 0
Stockholm
Country [24] 0 0
Switzerland
State/province [24] 0 0
Bern
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Glaxo Wellcome
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
PRIMARY: To evaluate the efficacy of valacyclovir hydrochloride (BW 256U87) in the prevention of cytomegalovirus (CMV) end-organ disease in HIV/CMV co-infected patients with CD4+ lymphocytes \< 100 cells/mm3. To assess the impact of BW 256U87, high-dose oral acyclovir and low-dose oral acyclovir on survival.

SECONDARY: To evaluate the effect of BW 256U87 on quality of life, the safety of the drug administered concurrently with standard antiretroviral agents and other essential therapies for the treatment and prevention of opportunistic diseases, and the efficacy of BW 256U87 in suppressing activation of other herpesviruses. To evaluate serologic and virologic risk factors for the development of CMV disease, including assessment of HIV activation, and the risk of developing drug-resistant CMV, HSV, and VZV.

Gastrointestinal absorption of acyclovir is not high enough to prevent CMV disease in patients with advanced HIV disease, although there is evidence that high doses of the drug may extend survival. Valacyclovir, a prodrug that is rapidly converted to acyclovir after oral administration, has a higher absorption rate and may therefore provide inhibitory activity against CMV.
Trial website
https://clinicaltrials.gov/study/NCT00001038
Trial related presentations / publications
Feinberg JE, Hurwitz S, Cooper D, Sattler FR, MacGregor RR, Powderly W, Holland GN, Griffiths PD, Pollard RB, Youle M, Gill MJ, Holland FJ, Power ME, Owens S, Coakley D, Fry J, Jacobson MA. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. J Infect Dis. 1998 Jan;177(1):48-56. doi: 10.1086/513804.
Fry J, Coakley D, Power M, Feinberg J. International collaborative clinical trials: the ACTG 204 experience. Int Conf AIDS. 1996 Jul 7-12;11(2):276 (abstract no ThB4146)
Griffiths PD, Feinberg J. Detection of cytomegalovirus in samples from patients enrolled in ACTG 204 / Glaxo Wellcome 123-014. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:54
Brosgart C, Fisher E, Pulling C, Chaloner K, Cohn D, Elsadr W, Verheggen R, Schmetter B, Alston B. Prevalence of asymptomatic CMV retinitis (CMVR) in AIDS patients. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:152 (abstract no 453)
Fisher E, Brosgart C, Cohn D, Chaloner K, Pulling C, Alston B, Schmetter B, El-Sadr W. Placebo (PLC)-controlled, multicenter trial of adefovir dipivoxil (ADV) in patients (pt) with HIV disease. . Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:160 (abstract no 491)
Feinberg JE, Bell WR, Chulay JD. A thrombotic microangiopathy (TMA)-like syndrome in patients with advanced HIV disease in a cytomegalovirus (CMV) prophylaxis trial (ACTG 204). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:196 (abstract no 715)
Sprenger HG, Law G, Pastoor G, Postma S, Schirm J, Weits J, The TH. Cytomegalovirus antigenemia (CMVAg) compared with other CMV tests during phase III study of valaciclovir (VACV) for CMV prophylaxis in advanced HIV disease (ACTG 204 study). Int Conf AIDS. 1996 Jul 7-12;11(2):285 (abstract no ThB4200)
Bell WR, Chulay JD, Feinberg JE. Manifestations resembling thrombotic microangiopathy in patients with advanced human immunodeficiency virus (HIV) disease in a cytomegalovirus prophylaxis trial (ACTG 204). Medicine (Baltimore). 1997 Sep;76(5):369-80. doi: 10.1097/00005792-199709000-00004. No abstract available.
Emery V, Sabin C, Feinberg J, Grywacz M, Knight S, Griffiths P. Quantitative effects of valaciclovir on the replication of cytomegalovirus in patients with advanced HIV disease. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:153 (abstract no 459)
Weinberg A, Schneider SA, Clark JC. Acyclovir (ACV) and valacyclovir (VAL) prophylaxis of AIDS patients does not alter cytomegalovirus (CMV) susceptibility to ganciclovir (GCV) or foscarnet (FOS). Program Abstr Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18:202 (abstract no I87)
Nokta MA, Holland F, De Gruttola V, Emery VC, Jacobson MA, Griffiths P, Pollard RB, Feinberg JE; AIDS Clinical Trials Group, Protocol 204/GlaxoWellcome 123-014, International CMV Prophylaxis Study Group. Cytomegalovirus (CMV) polymerase chain reaction profiles in individuals with advanced human immunodeficiency virus infection: relationship to CMV disease. J Infect Dis. 2002 Jun 15;185(12):1717-22. doi: 10.1086/340651. Epub 2002 May 31.
Public notes

Contacts
Principal investigator
Name 0 0
Feinberg J
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00001038