Cytomegalovirus RetinitisNCT00000989
The Safety and Effectiveness of Ganciclovir Used Alone or in Combination With Granulocyte-Macrophage Colony Stimulating Factor in the Treatment of Cytomegalovirus (CMV) of the Eye in Patients With AIDS
A study testing Zidovudine, Sargramostim and Ganciclovir in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
AMENDED: To evaluate the effect of sargramostim ( GM-CSF ) on modulating the granulocytopenia associated with concomitant DHPG and AZT therapy ( Phase B ), in terms of time to development of granulocytopenia as defined by an absolute neutrophil count ( ANC ) less than or equal to 750 cells/mm3. 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?
- Zidovudine, Sargramostim and Ganciclovir
- How many people
- 50 participants
- Where
- 4 sitesUnited States
- Study dates
- Start not givento Jul 1992
- Phase
- Interventional
- 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:
- Maintenance therapy for stable opportunistic infection which is not myelosuppressive.
- Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia.
- Acyclovir or other appropriate medications for appearance of Herpes simplex virus or Varicella zoster virus infections (after enrollment in study) that require systemic therapy.
- Medications absolutely necessary for the patient's welfare, at discretion of investigator.
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- Patients must:
- Have a diagnosis of sight-threatening cytomegalovirus (CMV) retinitis and AIDS.
- Have at least one pending culture for cytomegalovirus (CMV) from buffy coat and/or urine prior to study entry or previously documented CMV viremia or viruria within 6 weeks prior to study entry.
- Be capable of giving informed consent.
Who cannot join
- Co-existing Condition:
- Patients with the following are excluded:
- Corneal, lenticular, or vitreal opacification that precludes examination of the fundi, or evidence of other retinopathy other than cotton wool spots.
- Concurrent Medication:
- Excluded:
- Systemic antiviral therapy except Zidovudine (AZT) which will be added during the extended maintenance phase of the study.
Show all 20Show fewer
- Foscarnet.
- Treatment for an active AIDS-defining opportunistic infection.
- Any potentially cytotoxic chemotherapeutic agent.
- Patients with the following are excluded:
- Corneal, lenticular, or vitreal opacification that precludes examination of the fundi, or evidence of other retinopathy other than cotton wool spots.
- Prior Medication:
- Excluded within 14 days of study entry:
- Other immunomodulators, biologic response modifiers, or investigational agents.
- Protocol drugs.
- Foscarnet.
- Any potentially cytotoxic chemotherapeutic agent.
- Prior Treatment:
- Excluded within 14 days of study entry:
- Administration of cytomegalovirus hyperimmune globulin in therapeutic doses.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, 02215
Unc Aids Crs
Chapel Hill, North Carolina, 275997215
UCLA CARE Center CRS
Los Angeles, California, 90095
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, 10021
About this study
Official title: A Controlled, Randomized Phase II Study of the Safety and Efficacy of Combined Therapy With Ganciclovir and Granulocyte-Macrophage Colony Stimulating Factor Versus Ganciclovir Alone for the Treatment of Sight-Threatening Cytomegalovirus Retinitis in AIDS Patients
AMENDED: To evaluate the effect of sargramostim ( GM-CSF ) on modulating the granulocytopenia associated with concomitant DHPG and AZT therapy ( Phase B ), in terms of time to development of granulocytopenia as defined by an absolute neutrophil count ( ANC ) less than or equal to 750 cells/mm3.
Original design: To determine if granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is helpful in preventing the decreased numbers of white blood cells (infection-fighting cells) associated with ganciclovir ( DHPG ) therapy and to determine if GM-CSF can be safely used in AIDS patients with cytomegalovirus ( CMV ) retinitis.
AMENDED: In ACTG 004, among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy (5 mg/kg, 5x/week) with stable white blood cells (WBC)/absolute neutrophil counts (ANC) 7 (64 percent) required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT (600 mg/day) was added. A mean nadir ANC of 717 cells/ml was reached at a mean of 5 weeks of concomitant DHPG/AZT therapy in these patients. While recovery of depressed ANC occurred following discontinuation of study medications, progressive CMV infection (most commonly retinitis) occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption. Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPG/AZT. Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions. The study investigators concluded that the main, treatment limiting toxicity of combination DHPG/AZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia. In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy, extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol. Original design: CMV infection causes inflammation of the retina and can lead to permanent blindness. Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease. During DHPG treatment, however, about 30 to 55 percent of patients develop decreased white blood cell counts. GM-CSF, a naturally occurring human hormone, stimulates the body's bone marrow to produce more white blood cells. Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients.
Read the detailed description
AMENDED: In ACTG 004, among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy (5 mg/kg, 5x/week) with stable white blood cells (WBC)/absolute neutrophil counts (ANC) 7 (64 percent) required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT (600 mg/day) was added. A mean nadir ANC of 717 cells/ml was reached at a mean of 5 weeks of concomitant DHPG/AZT therapy in these patients. While recovery of depressed ANC occurred following discontinuation of study medications, progressive CMV infection (most commonly retinitis) occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption. Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPG/AZT. Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions. The study investigators concluded that the main, treatment limiting toxicity of combination DHPG/AZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia. In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy, extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol. Original design: CMV infection causes inflammation of the retina and can lead to permanent blindness. Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease. During DHPG treatment, however, about 30 to 55 percent of patients develop decreased white blood cell counts. GM-CSF, a naturally occurring human hormone, stimulates the body's bone marrow to produce more white blood cells. Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients.
AMENDED: Following completion of Phase A, study participants may elect to extend their assigned maintenance therapy (DHPG alone or DHPG/GM-CSF) in combination with AZT therapy (Phase B). GM-CSF dosing will be titrated as above to maintain a target ANC of 2500-5000 cells/mm3. Those patients receiving DHPG/AZT who develop neutropenia (ANC less than 750/ml) on two occasions will begin GM-CSF to maintain a target ANC of 2500-5000 cells/mm3. A similar schedule of clinical, ophthalmologic and laboratory evaluations will be followed in order to determine the efficacy and safety of extended maintenance therapy combined with AZT. Close monitoring of antiviral (CMV, HIV) and immunomodulatory activity will be assessed. This second phase of the study will last for an additional 52 weeks. AMENDED: Extended to 68 weeks. Original design: Patients are hospitalized for a minimum of 7 days to begin treatment for CMV retinitis. They are randomly assigned to one of two groups to receive DHPG either with or without GM-CSF. DHPG is given by intravenous infusion every 12 hours for the first 14 days. DHPG maintenance therapy is then given once a day, 7 days/week for the remaining 14 weeks of the study. For patients in the DHPG with GM-CSF group, the GM-CSF is given by subcutaneous injection for the 16 weeks of the study.
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Being tested
- Zidovudine, Sargramostim, Ganciclovir
- Keywords
- Retinitis, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Zidovudine
- Medical subject headings
- Cytomegalovirus Retinitis, HIV Infections, Retinitis, 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.
ZidovudineDrug
SargramostimDrug
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 completionJul 1992
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 N/A
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Schering-Plough, Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Hardy WD, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000989
- Sponsor's protocol ID
- ACTG 073
- Other IDs
- 11047
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
Hardy D, et al. Ganciclovir (GCV) and granulocyte-macrophage colony stimulating factor (GM-CSF) vs GCV alone as treatment for cytomegalovirus (CMV) retinitis (ACTG 073). Int Conf AIDS. 1992 Jul 19-24;8(1):Mo5 (abstract no MoA 0005)
Hardy D, Spector S, Polsky B, Crumpacker C, van der Horst C, Holland G, Freeman W, Heinemann MH, Sharuk G, Klystra J, et al. Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 2:S34-40. doi: 10.1007/BF01973600.
PubMed 7875151Hardy WD. Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. J Acquir Immune Defic Syndr (1988). 1991;4 Suppl 1:S22-8.
PubMed 1848618
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 Controlled, Randomized Phase II Study of the Safety and Efficacy of Combined Therapy With Ganciclovir and Granulocyte-Macrophage Colony Stimulating Factor Versus Ganciclovir Alone for the Treatment of Sight-Threatening Cytomegalovirus Retinitis in AIDS Patients
- ClinicalTrials.gov ID
- NCT00000989
- Acronym / sponsor ID
- ACTG 073
- Conditions
- Cytomegalovirus Retinitis, HIV Infections
- Keywords
- Retinitis, Ganciclovir, Drug Evaluation, Drug Therapy, Combination, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome, Zidovudine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Schering-Plough, Hoffmann-La Roche
- Study completion
- Jul 1992 (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.
AMENDED: To evaluate the effect of sargramostim ( GM-CSF ) on modulating the granulocytopenia associated with concomitant DHPG and AZT therapy ( Phase B ), in terms of time to development of granulocytopenia as defined by an absolute neutrophil count ( ANC ) less than or equal to 750 cells/mm3.
Original design: To determine if granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is helpful in preventing the decreased numbers of white blood cells (infection-fighting cells) associated with ganciclovir ( DHPG ) therapy and to determine if GM-CSF can be safely used in AIDS patients with cytomegalovirus ( CMV ) retinitis.
AMENDED: In ACTG 004, among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy (5 mg/kg, 5x/week) with stable white blood cells (WBC)/absolute neutrophil counts (ANC) 7 (64 percent) required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT (600 mg/day) was added. A mean nadir ANC of 717 cells/ml was reached at a mean of 5 weeks of concomitant DHPG/AZT therapy in these patients. While recovery of depressed ANC occurred following discontinuation of study medications, progressive CMV infection (most commonly retinitis) occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption. Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPG/AZT. Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions. The study investigators concluded that the main, treatment limiting toxicity of combination DHPG/AZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia. In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy, extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol. Original design: CMV infection causes inflammation of the retina and can lead to permanent blindness. Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease. During DHPG treatment, however, about 30 to 55 percent of patients develop decreased white blood cell counts. GM-CSF, a naturally occurring human hormone, stimulates the body's bone marrow to produce more white blood cells. Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients.
Detailed description
AMENDED: In ACTG 004, among 11 AIDS patients with CMV infection receiving DHPG maintenance therapy (5 mg/kg, 5x/week) with stable white blood cells (WBC)/absolute neutrophil counts (ANC) 7 (64 percent) required dose reduction or discontinuation of both antiviral medications due to granulocytopenia when AZT (600 mg/day) was added. A mean nadir ANC of 717 cells/ml was reached at a mean of 5 weeks of concomitant DHPG/AZT therapy in these patients. While recovery of depressed ANC occurred following discontinuation of study medications, progressive CMV infection (most commonly retinitis) occurred in 19 of 40 patients and seemed to be associated with DHPG therapy interruption. Only 3 of 40 patients were able to tolerate the complete 16 week study duration of DHPG/AZT. Pharmacokinetic studies of co-administration of DHPG and AZT revealed no significant drug-drug interactions. The study investigators concluded that the main, treatment limiting toxicity of combination DHPG/AZT therapy is granulocytopenia and that many patients treated on this study developed intercurrent OIs or staphylococcal septicemia. In order to determine whether patients receiving maintenance DHPG therapy with or without GM-CSF can tolerate concomitant AZT therapy, extended maintenance therapy with the assigned study regimen in combination with AZT will be incorporated into this protocol. Original design: CMV infection causes inflammation of the retina and can lead to permanent blindness. Treatment for CMV retinitis with DHPG has been shown to be effective in halting the progression of retinal disease. During DHPG treatment, however, about 30 to 55 percent of patients develop decreased white blood cell counts. GM-CSF, a naturally occurring human hormone, stimulates the body's bone marrow to produce more white blood cells. Studies with GM-CSF in AIDS patients have shown that it can significantly increase depressed white blood cell counts in these patients.
AMENDED: Following completion of Phase A, study participants may elect to extend their assigned maintenance therapy (DHPG alone or DHPG/GM-CSF) in combination with AZT therapy (Phase B). GM-CSF dosing will be titrated as above to maintain a target ANC of 2500-5000 cells/mm3. Those patients receiving DHPG/AZT who develop neutropenia (ANC less than 750/ml) on two occasions will begin GM-CSF to maintain a target ANC of 2500-5000 cells/mm3. A similar schedule of clinical, ophthalmologic and laboratory evaluations will be followed in order to determine the efficacy and safety of extended maintenance therapy combined with AZT. Close monitoring of antiviral (CMV, HIV) and immunomodulatory activity will be assessed. This second phase of the study will last for an additional 52 weeks. AMENDED: Extended to 68 weeks. Original design: Patients are hospitalized for a minimum of 7 days to begin treatment for CMV retinitis. They are randomly assigned to one of two groups to receive DHPG either with or without GM-CSF. DHPG is given by intravenous infusion every 12 hours for the first 14 days. DHPG maintenance therapy is then given once a day, 7 days/week for the remaining 14 weeks of the study. For patients in the DHPG with GM-CSF group, the GM-CSF is given by subcutaneous injection for the 16 weeks of the study.
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 (10 listed)
- Maintenance therapy for stable opportunistic infection which is not myelosuppressive.
- Aerosolized pentamidine for prophylaxis of Pneumocystis carinii pneumonia.
- Acyclovir or other appropriate medications for appearance of Herpes simplex virus or Varicella zoster virus infections (after enrollment in study) that require systemic therapy.
- Medications absolutely necessary for the patient's welfare, at discretion of investigator.
- Have a diagnosis of sight-threatening cytomegalovirus (CMV) retinitis and AIDS.
Key exclusion criteria (20 listed)
- Corneal, lenticular, or vitreal opacification that precludes examination of the fundi, or evidence of other retinopathy other than cotton wool spots.
- Systemic antiviral therapy except Zidovudine (AZT) which will be added during the extended maintenance phase of the study.
- Foscarnet.
- Treatment for an active AIDS-defining opportunistic infection.
- Any potentially cytotoxic chemotherapeutic 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 |
|---|---|---|
| Zidovudine | Drug | – |
| Sargramostim | 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.
- BackgroundHardy D, et al. Ganciclovir (GCV) and granulocyte-macrophage colony stimulating factor (GM-CSF) vs GCV alone as treatment for cytomegalovirus (CMV) retinitis (ACTG 073). Int Conf AIDS. 1992 Jul 19-24;8(1):Mo5 (abstract no MoA 0005)
- Background: PubMed 7875151Hardy D, Spector S, Polsky B, Crumpacker C, van der Horst C, Holland G, Freeman W, Heinemann MH, Sharuk G, Klystra J, et al. Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. Eur J Clin Microbiol Infect Dis. 1994;13 Suppl 2:S34-40. doi: 10.1007/BF01973600.
- Background: PubMed 1848618Hardy WD. Combined ganciclovir and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. J Acquir Immune Defic Syndr (1988). 1991;4 Suppl 1:S22-8.
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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.
Hardy WD study chair
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zidovudine, Sargramostim and Ganciclovir in people with Cytomegalovirus Retinitis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 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 10 inclusion and 20 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 4 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.
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 NCT00000989, which also lists 3 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.