24 Clinical Trials for Various Conditions
Cryptococcal meningitis is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in low and middle income countries where the ongoing HIV/AIDS pandemic increases the risk of cryptococcosis among persons living with HIV infection. The combination of amphotericin and flucytosine (5-FC) has been the mainstay of therapy for the initial management of cryptococcal meningitis for 4 decades. Indeed, the effective delivery of these first line therapy in Africa can lower mortality to 25%. However, several challenges exist. First, even while 5-FC is included on the WHO list of essential medicines, the availability of 5-FC worldwide is limited. Second, liposomal amphotericin (Ambisome ®) is currently available from a single source supplier, creating risk. Third, current therapies have substantial toxicity. Lastly, with widespread agricultural fungicide use of azoles, the median fluconazole minimum inhibitory concentration (MIC50 ) for Cryptococcus has doubled since 2013. Globally, new or improved antifungals are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions. As multiple new antifungal medicines are on the horizon, this platform trial utilizes a master protocol to investigate, multiple regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.
Cryptococcal meningitis (CM) is an infection of the membranes covering the brain and spinal cord, caused by the fungus Cryptococcus neoformans. CM most often affects people with compromised immune systems, like those with advanced HIV infection. This study explored the safety, tolerability, and therapeutic effect of a new treatment regimen with high-dose fluconazole for management of CM in HIV-infected patients.
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter efficacy and safety trial to evaluate Mycograb®. Subjects will be randomized to receive either Mycograb® (dosed 1 mg/kg) or placebo during the first week of induction therapy (amphotericin B plus 5-flucytosine) via a central line or peripheral venous line twice daily for 7 consecutive days. The total duration of the study will be approximately 24 months.
The purpose of this study is to examine the antifungal activity of recombinant interferon-gamma 1b (rIFN-gamma 1b) given with standard antifungal therapy.
To evaluate the safety of escalating doses of RMP-7 administered in persons with HIV infection and cryptococcal meningitis and to determine the MTD of the drug. To evaluate the pharmacokinetics, including cerebrospinal fluid (CSF) penetration, of amphotericin B when administered with RMP-7.
To evaluate the safety and effectiveness of fluconazole as treatment for acute cryptococcal meningitis in patients who have had an unsatisfactory response to or have experienced unacceptable toxicity with amphotericin B.
To compare the safety and effectiveness of fluconazole and amphotericin B, alone or in combination with flucytosine, as treatment for acute cryptococcal meningitis.
To compare the safety and effectiveness of fluconazole with that of placebo as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.
To evaluate and estimate the safety and efficacy of the combination of fluconazole and flucytosine as treatment for acute cryptococcal meningitis in patients with AIDS. Fluconazole and flucytosine have different mechanisms of action. Since fluconazole has not been associated with hematologic suppression and does not produce renal impairment that can result in higher serum flucytosine levels, this combination may be better tolerated than is amphotericin B plus flucytosine.
To evaluate the safety and effectiveness of fluconazole as an intravenous dose as initial treatment for acute cryptococcal meningitis followed by oral therapy in AIDS and non-AIDS patients. Lack of satisfactory response will allow increase of dose. Both newly diagnosed and relapsed patients are eligible.
To evaluate the safety and effectiveness of fluconazole as treatment for acute cryptococcal meningitis in AIDS patients. Both newly diagnosed and relapsed patients are eligible.
To compare the safety and effectiveness of fluconazole and amphotericin B, alone or in combination with flucytosine, as treatment for acute cryptococcal meningitis.
To compare the safety and effectiveness of fluconazole and amphotericin B as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.
To compare the safety and effectiveness of fluconazole and amphotericin B, alone or in combination with flucytosine, as treatment for acute cryptococcal meningitis.
To evaluate the safety and effectiveness of fluconazole as an intravenous dose as initial treatment for acute cryptococcal meningitis followed by oral therapy in AIDS and non-AIDS patients. Both newly diagnosed and relapsed patients are eligible. The effectiveness of maintenance fluconazole therapy in sustaining a clinical cure in AIDS patients will also be evaluated.
To evaluate the safety, tolerance and efficacy of three different dosage regimens of Amphotericin B Lipid Complex (ABLC) compared to Fungizone (Amphotericin B) in patients with AIDS and cryptococcal meningitis.
To evaluate the effect of corticosteroids on reducing elevated intracranial pressure in cryptococcal meningitis. To evaluate the safety of corticosteroids in patients with cryptococcal meningitis and intracranial hypertension. In AIDS patients with cryptococcal meningitis, a correlation has been found between early death and elevated intracranial pressure. Since dexamethasone has been found to reduce intracranial pressure resulting from other forms of meningitis, it may be of benefit in AIDS patients with cryptococcal meningitis.
To compare the safety and effectiveness of fluconazole (FCZ) and amphotericin B (AMB), alone or in combination with flucytosine (FLC), as treatment for acute cryptococcal meningitis in patients who have not been treated previously or who have relapsed after a previous successful treatment. Cryptococcal meningitis is an important cause of disease and death among patients with AIDS. Usually AMB is given either alone or with FLC to patients with this infection, but these treatments are not always effective and both have toxic effects. Animal studies and preliminary studies in humans show that FCZ is active in cryptococcal meningitis and suggest that it may be less toxic than either AMB or FLC.
To assess the safety and effectiveness of SCH 39304 as primary treatment of acute cryptococcal meningitis in HIV-infected patients. Safety and effectiveness of maintenance therapy following successful treatment of acute disease are also evaluated. Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis.
To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
This study will examine the effectiveness and safety of a combination treatment for cryptococcal meningitis, a fungal infection common in persons with acquired immune deficiency syndrome (AIDS) in the developing world. The standard initial treatment includes two medications: amphotericin B for 2 weeks followed by 8 weeks of fluconazole. This study will look at whether study participants recover more quickly and have fewer side effects if they are given both drugs at the same time for 2 weeks followed by 8 weeks of fluconazole as compared to the standard treatment. Participants will be followed for approximately 6 months from the time they are enrolled into the study.
Background: * Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases. Objectives: * To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity. * To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections. * To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time. * To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels. * To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL. * To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL. * To determine whether there is any association between ICL and autoimmunity. * To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients. Eligibility: * Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart. * Patients with negative results of HIV testing by ELISA, Western Blot, and viral load. * Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer. Design: * At the initial visit to the National Institutes of Health, the following evaluations will be conducted: * Personal and family medical histories. * Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies). * Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA. * Urinalysis and urine pregnancy testing for female patients of childbearing age. * Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies. * Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years. * Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.
The protocol will be carried out in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) and the following United States Code of Federal Regulations (CFR) applicable to clinical studies: 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812. NIH-funded investigators and study site staff who are responsible for the conduct, management, or oversight of NIH-funded studies have completed Human Subjects Protection and ICH GCP Training. The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the protocol and the consent form must be obtained before any participant is enrolled. Any amendment to the protocol will require review and approval by the IRB before the changes are implemented to the study. In addition, all changes to the consent form will be approved by the IRB; an IRB determination will be made regarding whether a new consent needs to be obtained from participants who provided consent, using a previously approved consent form.
To compare the safety and effectiveness of a new drug, fluconazole, with that of the usual therapy, amphotericin B, in the prevention of a relapse of cryptococcal meningitis (CM) in patients with AIDS who have been successfully treated for acute CM in the last 6 months. Cryptococcal meningitis is a life-threatening infectious complication of AIDS. Because relapse after treatment occurs in over 50 percent of cases, chronic maintenance therapy with intravenous (IV) amphotericin B is usually given. However, amphotericin B is not always effective, has toxic effects, and must be given by the intravenous route. Fluconazole is an antifungal agent that can be given orally and has been shown to be effective against cryptococcal infections in animals and against acute CM in a few AIDS patients. Also, the side effects experienced by over 2000 patients or volunteers given fluconazole have seldom been severe enough to require withdrawal of the drug.