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Cytomegalovirus InfectionsPhase 3NCT00001038

A Study of Valacyclovir Hydrochloride in the Prevention of Life-Threatening Cytomegalovirus Disease in HIV-Infected Patients

A Phase 3 study testing Valacyclovir hydrochloride and Acyclovir in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 35 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 13 years and older
Conditions the study is for
Cytomegalovirus Infections, HIV Infections
What is being tested?
Valacyclovir hydrochloride and Acyclovir
How many people
1,200 participants
Where
35 sitesin 10 countries
Study dates
Start not givento May 1996
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

35 sites in 10 countries.

35 sites in 10 countries

United States21 sites
  • Johns Hopkins Hosp

    Baltimore, Maryland, 212052196

  • Birmingham Veterans Administration Med Ctr

    Birmingham, Alabama, 35233

  • Harvard (Massachusetts Gen Hosp)

    Boston, Massachusetts, 02114

  • Boston Med Ctr

    Boston, Massachusetts, 02118

  • Univ of North Carolina School of Medicine

    Chapel Hill, North Carolina, 275997215

  • Northwestern Univ Med School

    Chicago, Illinois, 60611

  • Ohio State Univ Hosp Clinic

    Columbus, Ohio, 432101228

  • Univ of Colorado Health Sciences Ctr

    Denver, Colorado, 80262

  • Univ TX Galveston Med Branch

    Galveston, Texas, 775550882

  • Indiana Univ Hosp

    Indianapolis, Indiana, 462025250

  • Los Angeles County - USC Med Ctr

    Los Angeles, California, 90033

  • CARE Ctr / UCLA Med Ctr

    Los Angeles, California, 900951793

  • Yale Univ

    New Haven, Connecticut, 06519

  • Mount Sinai Med Ctr

    New York, New York, 10029

  • Highland Gen Hosp / San Francisco Gen Hosp

    Oakland, California, 946021018

  • Girard Med Ctr

    Philadelphia, Pennsylvania, 191046073

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • Kaiser Permanente Med Ctr

    San Francisco, California, 94115

  • Univ of Washington / Madison Clinic

    Seattle, Washington, 98122

  • Washington Univ

    St Louis, Missouri, 63110

  • North Central Bronx Hosp / Bronx Municipal Hosp

    The Bronx, New York, 10467

Other trials in United States

Canada5 sites
  • Southern Alberta HIV Clinic / Foothills Hosp

    Calgary, Alberta

  • Montreal Chest Institute

    Montreal, Quebec

  • Montreal Gen Hosp

    Montreal, Quebec

  • Sunnybrook Health Science Ctr

    Toronto, Ontario

  • Toronto Hosp

    Toronto, Ontario

Other trials in Canada

United Kingdom2 sites
  • Royal Free Hosp

    London

  • Westminster Hosp

    London

Other trials in United Kingdom

Australia1 site
  • Saint Vincent's Hosp Med Centre

    Sydney

Other trials in Australia

Denmark1 site
  • Hvidovre Univ Hosp

    Hvidore

Other trials in Denmark

France1 site
  • Services des Maladies Infectieuses

    Paris

Other trials in France

Germany1 site
  • Universitatsklinikum Rudolf Virchow

    Berlin

Other trials in Germany

Italy1 site
  • Universita Cattolica del Sacro Cuore

    Rome

Other trials in Italy

Sweden1 site
  • South Hosp

    Stockholm

Other trials in Sweden

Switzerland1 site
  • Medizinische Universibatspoliklinik Infekbiologie

    Bern

Other trials in Switzerland

About this study

Official 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)

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.

Read the detailed description

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.

Patients are randomized to receive BW 256U87 alone or acyclovir alone as control at either high-dose or low-dose. The acyclovir controls will provide suppressive therapy for herpes simplex infections and may affect survival.

Being tested
Valacyclovir hydrochloride, Acyclovir
Keywords
Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents
Medical subject headings
Cytomegalovirus Infections, HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Valacyclovir hydrochlorideDrug

  • AcyclovirDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Primary completionMay 1996

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Enrolment
1,200 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001038
Sponsor's protocol ID
ACTG 204
Other IDs
FDA 104C
Status last verified
Feb 2011
First submitted
2 Nov 1999
Last updated
1 Mar 2011
Results posted
No

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.

    PubMed 9419169
  • 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.

    PubMed 9352739
  • 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.

    PubMed 12085316

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Valacyclovir hydrochloride and Acyclovir in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 35 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Canada, United Kingdom, Australia, Denmark and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001038, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2011.

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