A Phase II Dose-Ranging, Open-Labelled Trial of Foscarnet Salvage Therapy for AIDS Patients With Sight-Threatening CMV Retinitis Who Cannot Be Treated With Ganciclovir Due To Myelosuppression or Treatment Failure
Foscarnet sodium
Infections transmises par le sang+32
+ Maladies génito-urinaires
+ Maladies Génitales
Étude thérapeutique
Résumé
Because of the seriousness of sight-threatening CMV retinitis in AIDS patients and a lack of other available treatments for those patients who cannot be treated with ganciclovir (DHPG) (because of its toxic effect on the body's blood-forming cells, because it did not control the disease, or because patient's blood cell or platelet counts are too low to begin with), it is worthwhile to try an immediate trial with foscarnet. AMENDED: ACTG 093 was originally designed as a randomized dose-ranging study of foscarnet maintenance therapy. Patients enrolled between March 17, 1989, and January 1, 1990, received either 60 mg/kg/day or 90/mg/kg day as maintenance therapy following the 2 week induction period. Based on the preliminary results of ACTG 015/915, which studied maintenance doses of foscarnet of 60 mg/kg/day, 90 mg/kg/day and 120 mg/kg/day, the 60-mg/kg/day and 90/mg/kg/day arms of this study have been closed. All patients entering the study beginning January 2, 1990 will receive foscarnet maintenance therapy on a 120/mg/kg/day algorithm following induction. AMENDED: The ACTG 093 optional extended maintenance therapy period will conclude on January 2, 1991 in order to facilitate timely analysis of this study. All patients who wish to continue foscarnet therapy should be referred to Astra Protocol 90-FOS-14 at telephone number 800-292-5775. Original design: Patients are placed into two groups: (1) patients who have a sight-threatening lesion in the retina of an eye with vision that can be saved (corrected vision of 20/100 or better) and who cannot be treated with DHPG, and (2) patients whose retinitis has quickly gotten worse and/or has shown resistance to DHPG treatment. Both groups will receive a beginning (induction) dose of foscarnet by vein (IV) for 2 weeks, followed by a maintenance dose for 8 weeks with an option to continue up to 24 weeks. AMENDED: Patients entering the study on or after 01/02/90 receive the standard two week course of foscarnet induction therapy and receive maintenance therapy. Treatment is given for a ten week study period or until progression occurs or toxicity endpoints are reached. If retinitis is stable and foscarnet well-tolerated, maintenance therapy may be extended for a period not to exceed 1 year.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.156 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.De 13 à 65 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis. Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Therapy with vancomycin. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Initiate or resume zidovudine (AZT) in 2nd week of foscarnet maintenance therapy at dose of 100 or 200 mg q4h at investigator's discretion. Initiate or continue erythropoietin therapy via the treatment IND mechanism. Initiate or continue therapy with investigational triazoles for disseminated fungal infections. Caution should be used in concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Prior Medication: Allowed: Oral antibiotics if patient is hematologically stable on that regimen for at least 30 days prior to study entry. Drug therapy for Kaposi's sarcoma if patient is hematologically stable for at least 30 days prior to study entry. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Karnofsky performance status = or < 50. Concurrent Medication: Excluded: Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). Ganciclovir. Didanosine (ddI). Systemic acyclovir. CMV hyperimmune serum / globulin. Interferons. Nephrotoxic agents including aminoglycosides, amphotericin B, parenteral pentamidine. Caution should be used in the concurrent use of foscarnet and ciprofloxacin, as such use has appeared to exacerbate renal failure in one patient. Patients with the following are excluded: Corneal, lens, or vitreous opacification that precludes examination of the fundi. Clinically significant pulmonary or neurologic impairment, including intubation or coma. Unwilling or unable to suspend zidovudine treatment until 2nd week of foscarnet maintenance therapy. Prior Medication: Excluded: Foscarnet for cytomegalovirus retinitis. Systemic acyclovir. Immunomodulators. Biologic response modifiers. Investigational agents (other than erythropoietin and investigational triazoles). AIDS patients with active cytomegalovirus (CMV) retinitis who cannot be treated with ganciclovir. At least one pending CMV culture from both blood (buffy-coat) and urine must be obtained prior to study entry. Patients must be able to give informed consent. Patients with a history of a seizure disorder or central nervous system mass lesion will be included.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 11 sites
Ucsf Aids Crs
San Francisco, United StatesUniv. of Miami AIDS CRS
Miami, United StatesJohns Hopkins Adult AIDS CRS
Baltimore, United States