Cytomegalovirus RetinitisPhase 2NCT00000697
A Study of Foscarnet in the Treatment of Cytomegalovirus (CMV) of the Eyes in Patients With AIDS Who Cannot Use Ganciclovir
A Phase 2 study testing Foscarnet sodium in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
Trial summary
To study the safety and effectiveness of foscarnet in the treatment of AIDS patients who have active infection with cytomegalovirus (CMV) that is causing inflammation of the retina (retinitis). Read more about this study
- Who is it for?
- Ages 13 to 65 years
- Conditions the study is for
- Cytomegalovirus Retinitis, HIV Infections
- What is being tested?
- Foscarnet sodium
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Start not givento not given
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Concurrent Medication:
- Allowed if hematologically stable on that regimen for at least 30 days prior to study entry:
- Oral antibiotics.
- Chemotherapy for Kaposi's sarcoma.
- Acyclovir for outbreaks of herpes simplex or shingles.
- Zidovudine (AZT), either initiated or continued, by patients randomized to both treatment arms. AZT given concurrently with foscarnet may be administered at a dose of 100 or 200 mg every 4 hours (q4h) at the investigator's discretion. Patients randomized to the delayed treatment arm may initiate or continue AZT administration at a dose of 100 or 200 mg q4h at the investigator's discretion. AZT may not be administered during the first 3 weeks of foscarnet therapy. Patients randomized to immediate therapy may begin or resume AZT when they enter the 2nd week of maintenance therapy (week 4 of the 10-week study period), if their hemoglobin is = or > 8 g/dl and absolute neutrophil count is = or > 1000 cells/mm3 at that time. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient.
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- Patients must have active AIDS-related cytomegalovirus (CMV) retinitis as identified by its characteristic ophthalmoscopic appearance and verified by fundus photography. Patients must also demonstrate one of the following clinical and/or laboratory findings:
- Treatment with ganciclovir (DHPG) resulting in dose-limiting toxicity (absolute neutrophil count (= polymorphonuclear leukocytes plus bands) < 500 cells/mm3 or platelets < 25000 platelets/mm3) occurring on = or > two documented occasions at least 7 days apart while receiving up to a maximum induction regimen of 10 mg/kg/day or a maintenance regimen of up to 5 mg/kg/day. Neutropenia should not be the result of zidovudine (AZT) treatment.
- Ineligibility for DHPG therapy because of baseline neutropenia (absolute neutrophil count < 500 cells/mm3) or thrombocytopenia (platelets < 25000 platelets/mm3) documented on = or > 2 occasions at least 7 days apart. Baseline myelosuppression should not be the result of ongoing therapy with either prescription drugs, including AZT, or over-the-counter medications.
- Prior Medication:
- Allowed:
- Zidovudine (AZT), according to protocol stipulations.
- Prophylaxis therapy for Pneumocystis carinii pneumonia (PCP).
- Chemotherapy for Kaposi's sarcoma.
Who cannot join
- Co-existing Condition:
- Patients with any of the following diseases or symptoms are excluded:
- An immediately sight-threatening lesion in a salvageable eye (i.e., patients who have a cytomegalovirus (CMV) lesion that is within 1500 microns of the optic disc or fovea in an eye with correction vision of 20/100 or better).
- Corneal, lens or vitreous opacification which precludes examination of the fundi of either eye.
- Any clinically significant pulmonary or neurologic impairment (i.e., patients who are intubated or comatose), although patients with a history of a seizure disorder or a central nervous system (CNS) mass lesion may be enrolled.
- Concurrent Medication:
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- Excluded:
- Systemic acyclovir as preventive therapy for herpes infection.
- Any nephrotoxic agent.
- Specifically excluded are aminoglycosides, amphotericin B, and parenteral pentamidine. A patient who requires such therapy must be temporarily discontinued from study therapy; if nephrotoxic therapy is given for > 7 days, the patient will be permanently withdrawn from study therapy.
- Other anti-cytomegalovirus (CMV) therapy, specifically ganciclovir, CMV hyperimmune serum/globulin, interferons, and immunomodulators.
- Patients will be excluded from the study if they are unwilling or unable to suspend zidovudine (AZT) treatment during the first 3 weeks of the study period (1) if randomized to the immediate treatment arm, or (2) when crossed-over from the delayed treatment arm to foscarnet therapy because of retinitis progression.
- Prior Medication:
- Excluded:
- Foscarnet for cytomegalovirus (CMV) retinitis.
- Excluded within 7 days of study entry:
- Immunomodulators.
- Investigational agents other than ganciclovir.
About this study
Official title: A Phase II Randomized Controlled Trial of Immediate Versus Delayed Foscarnet Therapy in AIDS Patients With Non-Immediately Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due to Myelosuppression
To study the safety and effectiveness of foscarnet in the treatment of AIDS patients who have active infection with cytomegalovirus (CMV) that is causing inflammation of the retina (retinitis). In addition, these patients cannot be treated with ganciclovir (DHPG) because of its toxic effect on the body's blood-forming cells or because white blood cell or platelet counts were too low.
CMV is a common virus, which can cause blindness and death in AIDS patients. Previous studies demonstrate that foscarnet has been effective in both AIDS and non-AIDS patients with CMV infection. Although treatment with ganciclovir (DHPG) is also effective, a significant toxicity leading to dose-limiting neutropenia (low white blood cell count) in one third of treated patients has been associated with the drug. Based on the serious nature of CMV retinitis and the lack of alternative drug therapies for DHPG-sensitive patients, the present study will evaluate the safety and efficacy of intravenous (IV) foscarnet in AIDS patients with CMV retinitis.
Read the detailed description
CMV is a common virus, which can cause blindness and death in AIDS patients. Previous studies demonstrate that foscarnet has been effective in both AIDS and non-AIDS patients with CMV infection. Although treatment with ganciclovir (DHPG) is also effective, a significant toxicity leading to dose-limiting neutropenia (low white blood cell count) in one third of treated patients has been associated with the drug. Based on the serious nature of CMV retinitis and the lack of alternative drug therapies for DHPG-sensitive patients, the present study will evaluate the safety and efficacy of intravenous (IV) foscarnet in AIDS patients with CMV retinitis.
Following routine evaluation studies, patients are randomized to receive foscarnet right away or to delay treatment, as their retinitis has been determined not to be immediately sight-threatening. Patients are hospitalized for the first 3 days and may remain hospitalized for as many as 14 days. Foscarnet is given by vein (IV) in what is called induction therapy, and if the patient's retinitis stabilizes after 2 weeks of treatment, treatment with foscarnet is continued in maintenance therapy for another 8 weeks. During maintenance therapy, patients receive salt solution IV to help prevent any toxic side effect of foscarnet on the kidneys. Patients have regular checkups to monitor their retinitis as well as their general health. Patients taking zidovudine (AZT) prior to entering the study may continue their treatment if they are selected for the delayed treatment group; if they are selected for the immediate treatment group, they begin or resume AZT therapy when they enter the 2nd week of maintenance therapy. Patients are followed as outpatients for at least 10 weeks, with clinic check-ups and lab tests once every week; eye exams are done once a week for the first 2 weeks and then every other week. If clinically indicated, a continued maintenance regimen may be administered after the 10th week; the total duration of therapy plus maintenance is not to exceed 24 weeks. Note: Patients scheduled for the delayed foscarnet treatment are immediately given foscarnet at the first sign that their retinitis is getting worse.
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Being tested
- Foscarnet sodium
- Keywords
- Retinitis, AIDS-Related Opportunistic Infections, Bone Marrow, Ganciclovir, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents
- 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
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)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 2
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- MA Jacobson, Study chairCS Crumpacker, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000697
- Sponsor's protocol ID
- ACTG 092
- Other IDs
- 11067
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Polis MA. Foscarnet and ganciclovir in the treatment of cytomegalovirus retinitis. J Acquir Immune Defic Syndr (1988). 1992;5 Suppl 1:S3-10.
PubMed 1318365
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 II Randomized Controlled Trial of Immediate Versus Delayed Foscarnet Therapy in AIDS Patients With Non-Immediately Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due to Myelosuppression
- ClinicalTrials.gov ID
- NCT00000697
- Acronym / sponsor ID
- ACTG 092
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Keywords
- Retinitis, AIDS-Related Opportunistic Infections, Bone Marrow, Ganciclovir, Foscarnet, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Antiviral Agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- 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 study the safety and effectiveness of foscarnet in the treatment of AIDS patients who have active infection with cytomegalovirus (CMV) that is causing inflammation of the retina (retinitis). In addition, these patients cannot be treated with ganciclovir (DHPG) because of its toxic effect on the body's blood-forming cells or because white blood cell or platelet counts were too low.
CMV is a common virus, which can cause blindness and death in AIDS patients. Previous studies demonstrate that foscarnet has been effective in both AIDS and non-AIDS patients with CMV infection. Although treatment with ganciclovir (DHPG) is also effective, a significant toxicity leading to dose-limiting neutropenia (low white blood cell count) in one third of treated patients has been associated with the drug. Based on the serious nature of CMV retinitis and the lack of alternative drug therapies for DHPG-sensitive patients, the present study will evaluate the safety and efficacy of intravenous (IV) foscarnet in AIDS patients with CMV retinitis.
Detailed description
CMV is a common virus, which can cause blindness and death in AIDS patients. Previous studies demonstrate that foscarnet has been effective in both AIDS and non-AIDS patients with CMV infection. Although treatment with ganciclovir (DHPG) is also effective, a significant toxicity leading to dose-limiting neutropenia (low white blood cell count) in one third of treated patients has been associated with the drug. Based on the serious nature of CMV retinitis and the lack of alternative drug therapies for DHPG-sensitive patients, the present study will evaluate the safety and efficacy of intravenous (IV) foscarnet in AIDS patients with CMV retinitis.
Following routine evaluation studies, patients are randomized to receive foscarnet right away or to delay treatment, as their retinitis has been determined not to be immediately sight-threatening. Patients are hospitalized for the first 3 days and may remain hospitalized for as many as 14 days. Foscarnet is given by vein (IV) in what is called induction therapy, and if the patient's retinitis stabilizes after 2 weeks of treatment, treatment with foscarnet is continued in maintenance therapy for another 8 weeks. During maintenance therapy, patients receive salt solution IV to help prevent any toxic side effect of foscarnet on the kidneys. Patients have regular checkups to monitor their retinitis as well as their general health. Patients taking zidovudine (AZT) prior to entering the study may continue their treatment if they are selected for the delayed treatment group; if they are selected for the immediate treatment group, they begin or resume AZT therapy when they enter the 2nd week of maintenance therapy. Patients are followed as outpatients for at least 10 weeks, with clinic check-ups and lab tests once every week; eye exams are done once a week for the first 2 weeks and then every other week. If clinically indicated, a continued maintenance regimen may be administered after the 10th week; the total duration of therapy plus maintenance is not to exceed 24 weeks. Note: Patients scheduled for the delayed foscarnet treatment are immediately given foscarnet at the first sign that their retinitis is getting worse.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 13 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Allowed if hematologically stable on that regimen for at least 30 days prior to study entry:
- Oral antibiotics.
- Chemotherapy for Kaposi's sarcoma.
- Acyclovir for outbreaks of herpes simplex or shingles.
- Zidovudine (AZT), either initiated or continued, by patients randomized to both treatment arms. AZT given concurrently with foscarnet may be administered at a dose of 100 or 200 mg every 4 hours (q4h) at the investigator's discretion. Patients randomized to the delayed treatment arm may initiate or continue AZT administration at a dose of 100 or 200 mg q4h at the investigator's discretion. AZT may not be administered during the first 3 weeks of foscarnet therapy. Patients randomized to immediate therapy may begin or resume AZT when they enter the 2nd week of maintenance therapy (week 4 of the 10-week study period), if their hemoglobin is = or > 8 g/dl and absolute neutrophil count is = or > 1000 cells/mm3 at that time. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient.
Key exclusion criteria (18 listed)
- An immediately sight-threatening lesion in a salvageable eye (i.e., patients who have a cytomegalovirus (CMV) lesion that is within 1500 microns of the optic disc or fovea in an eye with correction vision of 20/100 or better).
- Corneal, lens or vitreous opacification which precludes examination of the fundi of either eye.
- Any clinically significant pulmonary or neurologic impairment (i.e., patients who are intubated or comatose), although patients with a history of a seizure disorder or a central nervous system (CNS) mass lesion may be enrolled.
- Systemic acyclovir as preventive therapy for herpes infection.
- Any nephrotoxic agent.
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 | – |
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Background: PubMed 1318365Polis MA. Foscarnet and ganciclovir in the treatment of cytomegalovirus retinitis. J Acquir Immune Defic Syndr (1988). 1992;5 Suppl 1:S3-10.
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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.
MA Jacobson study chair
CS Crumpacker study chair
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Foscarnet sodium in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID).
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 14 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: withdrawn, 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.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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 NCT00000697, which also lists 1 linked publication.
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.