Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00000970
Other study ID # ACTG 151
Secondary ID 11126
Status Completed
Phase Phase 1
First received
Last updated
Est. completion date June 1993

Study information

Verified date October 2021
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To examine the safety and tolerance of the administration of ganciclovir and foscarnet given together or alternately; to determine the interactive pharmacokinetics (blood level) profile of long-term combined and alternating therapy with these two drugs. Additional objectives are to examine the effect of these treatments in controlling time to cytomegalovirus (CMV) retinitis progression and to examine the antiviral activity of combined and alternating ganciclovir/foscarnet treatment and development of antiviral resistance. 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date June 1993
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 13 Years and older
Eligibility Inclusion Criteria Concurrent Medication: Allowed: - 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: Allowed: - 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 drug. 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. Allowed: - 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: Excluded: - 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: Excluded: - Foscarnet or ganciclovir for CMV retinitis (excluding the 14-day induction period). Prior Treatment: Excluded: - Cytomegalovirus (CMV) hyperimmune globulin within 14 days prior to study entry.

Study Design


Intervention

Drug:
Foscarnet sodium

Ganciclovir


Locations

Country Name City State
United States Unc Aids Crs Chapel Hill North Carolina
United States USC CRS Los Angeles California
United States Memorial Sloan-Kettering Cancer Ctr. New York New York
United States Washington U CRS Saint Louis Missouri
United States Ucsf Aids Crs San Francisco California
United States University of Washington AIDS CRS Seattle Washington

Sponsors (3)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) Astra USA, Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

References & Publications (2)

Aweeka FT, Gambertoglio JG, Kramer F, van der Horst C, Polsky B, Jayewardene A, Lizak P, Emrick L, Tong W, Jacobson MA. Foscarnet and ganciclovir pharmacokinetics during concomitant or alternating maintenance therapy for AIDS-related cytomegalovirus retinitis. Clin Pharmacol Ther. 1995 Apr;57(4):403-12. — View Citation

Jacobson MA, Kramer F, Bassiakos Y, Hooton T, Polsky B, Geheb H, O'Donnell JJ, Walker JD, Korvick JA, van der Horst C. Randomized phase I trial of two different combination foscarnet and ganciclovir chronic maintenance therapy regimens for AIDS patients with cytomegalovirus retinitis: AIDS clinical Trials Group Protocol 151. J Infect Dis. 1994 Jul;170(1):189-93. — View Citation

See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1
Completed NCT05916989 - Stimulant Use and Methylation in HIV
Terminated NCT02116660 - Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) Phase 2