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A Phase I Open-Labeled Study of Long Term Combined or Alternating Foscarnet/Ganciclovir Maintenance Therapy for AIDS Patients With CMV Retinitis After Ganciclovir Induction Therapy

Phase 1
13 Years
Not Enrolling
Cytomegalovirus Retinitis, HIV Infections

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Trial Information

A Phase I Open-Labeled Study of Long Term Combined or Alternating Foscarnet/Ganciclovir Maintenance Therapy for AIDS Patients With CMV Retinitis After Ganciclovir Induction Therapy

Sight-threatening CMV retinitis occurs in at least 6 percent of AIDS patients. By 1991 (US),
there may be 6000 to 10000 patients with CMV retinitis. Many clinical reports suggest that
both ganciclovir (DHPG) and foscarnet have an antiviral effect against CMV that is often
associated with clinical stabilization. Effectiveness of ganciclovir and foscarnet is
correlated with weekly maintenance and since toxicity is dose-limiting in up to 20 percent
of patients receiving either drug for long periods, it may be beneficial in long-term
maintenance treatment to combine or alternate these two drugs at a lower total weekly dose
of each drug.

This strategy may result in a greater net antiviral effect with less toxicity than is seen
with either drug alone, because the toxicities of each drug are quite different.

All patients have newly diagnosed CMV retinitis and have completed a 14-day course of
intravenous ganciclovir or foscarnet induction therapy within 1 week prior to study entry.
The maintenance period consists of a 12-week study period followed by a 40 week follow-up
period. Treatment consists of either combined sequential daily maintenance therapy of both
foscarnet and ganciclovir or alternating daily treatment with ganciclovir one day and
foscarnet the following day.

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:


- Chemotherapy for Kaposi's sarcoma (excluding interferon) if patient is
hematologically stable for at least 30 days prior to entry.

- Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) after first two weeks
of study period if absolute neutrophil count is > 1000 cells/mm3 and hemoglobin = or
> 8 g/dl.

- Vancomycin.

- Fluconazole or investigational triazoles (e.g., itraconazole, SCH 39304) for
disseminated fungal infection.

- Pneumocystis carinii pneumonia prophylaxis (except parenteral pentamidine).

- Acyclovir or other appropriate medication may be instituted in the event of the
appearance of Herpes simplex virus

- (HSV) or Varicella zoster virus (VZV) infections.

- G-CSF or GM-CSF for grade 4 neutropenia.

Concurrent Treatment:


- Recombinant human erythropoietin.

Prior Medication: Required:

- Completion of 14-day course of intravenous ganciclovir induction therapy (2.5 mg/kg
IV q8h or 5 mg/kg q12h for 14 days) or foscarnet induction therapy (60 mg/kg q8h
adjusted for renal function for 14 days) within 1 week prior to study entry. Patients
who do not initiate the study immediately upon completing ganciclovir induction
therapy should receive a maintenance ganciclovir regimen of 5 mg/kg/day or 6
mg/kg/day 5 x week or a foscarnet regimen of 90-120 mg/kg/day until initiating study

Patients must:

- Have a diagnosis of cytomegalovirus retinitis and HIV infection.

- Be capable of giving informed consent. Patients < 18 years of age may participate
with the consent of parent, guardian, or person with power of attorney.


- History of seizure disorder or a central nervous system (CNS) mass lesion.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

- Evidence of tuberculous, diabetic or hypertensive retinopathy.

- Osteomalacia, neoplasm metastatic to bone or other bone disease.

- Any clinically significant pulmonary or neurologic impairment (for example, patients
who are intubated or comatose).

- Retinal detachment.

- Corneal, lens, or vitreous opacification precluding funduscopic exam.

Concurrent Medication:


- Immunomodulators, biologic response modifiers or investigational agents not
specifically allowed.

- Aminoglycosides, amphotericin B, probenecid, parenteral pentamidine.

- Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) until completion of
second week of maintenance therapy. ddC use is discouraged but not prohibited
because of paucity of experience of this drug with ganciclovir and foscarnet.

Anti-cytomegalovirus (CMV) therapy:

- Ganciclovir, CMV hyperimmune serum/globulin, interferons, immunomodulators.

- Prophylactic antiviral therapy with acyclovir.

Patients with the following are excluded:

- Active AIDS-defining opportunistic infection requiring therapy that is currently
causing nephrotoxicity or myelosuppression.

- Known hypersensitivity to either of the study therapies.

Prior Medication:


- Foscarnet or ganciclovir for CMV retinitis (excluding the 14-day induction period).

Prior Treatment:


- Cytomegalovirus (CMV) hyperimmune globulin within 14 days prior to study entry.

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Jacobson MA

Investigator Role:

Study Chair


United States: Federal Government

Study ID:

ACTG 151



Start Date:

Completion Date:

June 1993

Related Keywords:

  • Cytomegalovirus Retinitis
  • HIV Infections
  • Retinitis
  • AIDS-Related Opportunistic Infections
  • Ganciclovir
  • Drug Evaluation
  • Drug Therapy, Combination
  • Foscarnet
  • Cytomegalovirus Infections
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Retinitis
  • Cytomegalovirus Retinitis



USC CRS Los Angeles, California  90033
Ucsf Aids Crs San Francisco, California  
Washington U CRS St. Louis, Missouri  
Memorial Sloan-Kettering Cancer Ctr. New York, New York  10021
Unc Aids Crs Chapel Hill, North Carolina  27599
University of Washington AIDS CRS Seattle, Washington  98122