Cytomegalovirus RetinitisPhase 1NCT00000970
A Study of Foscarnet Plus Ganciclovir in the Treatment of Cytomegalovirus of the Eye in Patients With AIDS Who Have Already Been Treated With Ganciclovir
A Phase 1 study testing Foscarnet sodium and Ganciclovir in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Cytomegalovirus Retinitis, HIV Infections
- What is being tested?
- Foscarnet sodium and Ganciclovir
- How many people
- 30 participants
- Where
- 6 sitesUnited States
- Study dates
- Start not givento Jun 1993
- Phase
- Phase 1
- 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:
- 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.
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Unc Aids Crs
Chapel Hill, North Carolina, 27599
USC CRS
Los Angeles, California, 90033
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, 10021
Ucsf Aids Crs
San Francisco, California
University of Washington AIDS CRS
Seattle, Washington, 98122
Washington U CRS
St Louis, Missouri
About this study
Official title: 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
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.
Read the detailed 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.
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Being tested
- Foscarnet sodium, Ganciclovir
- Keywords
- Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome
- Medical subject headings
- Cytomegalovirus Retinitis, HIV Infections, Retinitis, AIDS-Related Opportunistic Infections, Multiple Acyl Coenzyme A Dehydrogenase Deficiency, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Foscarnet sodiumDrug
GanciclovirDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionJun 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus RetinitisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Astra USA, Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Jacobson MA, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000970
- Sponsor's protocol ID
- ACTG 151
- Other IDs
- 11126
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
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. doi: 10.1093/infdis/170.1.189.
PubMed 8014496Aweeka 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. doi: 10.1016/0009-9236(95)90209-0.
PubMed 7712668
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00000970
- Acronym / sponsor ID
- ACTG 151
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Keywords
- Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Astra USA, Hoffmann-La Roche
- Study completion
- Jun 1993 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- 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).
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Foscarnet sodium | Drug | – |
| Ganciclovir | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Background: PubMed 8014496Jacobson 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. doi: 10.1093/infdis/170.1.189.
- Background: PubMed 7712668Aweeka 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. doi: 10.1016/0009-9236(95)90209-0.
Related trials for Cytomegalovirus Retinitis
Recruiting
Evaluation of Safety and Efficacy of Autologous LB-DTK-CMV in Patients With Antiviral-Resistant and Refractory Cytomegalovirus Retinitis.
CMV Retinitis
RecruitingEarly Phase 1
Clinical Study of High Concentration Ganciclovir Eye Drops in the Treatment of Cytomegalovirus Retinitis
Cytomegalovirus Retinitis, Ganciclovir Eye Drops
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacobson MA study chair
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Foscarnet sodium and Ganciclovir in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.
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 20 inclusion and 24 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 NCT00000970, which also lists 2 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 4 Nov 2021.