Field assays with anti-malarial vaccines: phase III protocols.
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “Clinical Trials, Phase III as Topic”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Phase II and III studies with carboplatin in small cell lung cancer.
Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (11% complete response [CR], 59% CR plus partial response [PR]). Combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease (LD), with 52% CRs. The median survival time with this combination was 14 months in patients with LD and 9.5 months in those with extensive disease (ED). The 30-month survival rates are 30% in LD and 10% in ED, which represents a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in ED patients, CR and overall response rates to date are higher in the CEV arm (CR, 20% versus 15%; CR plus PR, 83% versus 65%), but as yet the differences are not statistically significant. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial are presented.
Adult↗
Antiemetic study design: desirable objectives, stratifications and analyses.
Once the optimal dose and safety of an antiemetic has been established a randomised double blind parallel subjects design is recommended for phase III studies. Randomisation distributes the unknown prognostic variables so that their effects can be allowed for in tests for statistical significance. Stratification can equally distribute the known prognostic factors e.g. prior exposure to chemotherapy, strength of the emetic stimulus, age, sex and prior alcohol consumption. A cross-over design is often proposed because less patients would be required to achieve the same power as a parallel subjects study. The major problem with this design is in being able to estimate and allow for carry over effects or treatment period interactions which can interact with each other and the direct treatment effect. The study must be large enough to detect a statistically significant difference of clinical importance. Interim analyses should be preplanned and early termination should require a difference between the arms with a more significant P value than 0.05. Simple evaluation of efficacy could include quantitation of objective parameters and use of simple ordinal scales to record more subjective phenomena. In a parallel subjects design patients must assess their overall tolerance of therapy which balances the antiemetic's efficacy and toxicity.
Antiemetics↗
[Methodology in clinical trials of anti-arrhythmia agents in ventricular arrhythmias. Analysis and perspective following results of the CAST study].
The results of the Cardiac Arrhythmia Suppression Trial (CAST) have not finished modifying the methodology and strategy of development of new antiarrhythmic agents for the treatment of ventricular arrhythmias. The demonstration of a dissociation between a proved antiarrhythmic effect and increased mortality in coronary patients treated with encainide or flecainide, means that, in this situation, antiarrhythmic efficacy cannot be considered to be a substitute criterion of therapeutic benefit. The consequences of these results are as follows: in phase II, the dose-effect relationships should be studied in patients with chronic ventricular extrasystole without ischemic heart disease. This model is sufficiently predictive for the selection of the dosage to be tested in phase III; in phase III, studies of benign ventricular arrhythmias, antiarrhythmic efficacy is demonstrated by ambulatory ECG recordings. If these studies include patients with ischemic heart disease, the patients must be placed on betablocker therapy and the benefits in terms of reduction of mortality have to be shown by controlled trials versus placebo. In malignant life-threatening arrhythmias, open clinical trials may be performed using provocative electrophysiological studies. The inclusion of patients with implanted automatic defibrillator devices could constitute control groups for the placebo group. The future of antiarrhythmic agents for the treatment of ventricular arrhythmias greatly depends on the search for criteria of severity of arrhythmias and the validation of intermediate criteria of efficacy.
Anti-Arrhythmia Agents↗
Evaluation of new anti-infective drugs for the treatment of chancroid. Infectious Diseases Society of America and the Food and Drug Administration.
Chancroid is a mucocutaneous infection caused by Haemophilus ducreyi that produces ulcerative lesions and enhances the efficiency of transmission of human immunodeficiency virus (HIV). Confirmation of infection by culture of H. ducreyi is essential in therapeutic trials. Minimal inhibitory concentrations of antibiotics for the isolate should be determined by agar dilution. Patients should be evaluated by appropriate laboratory tests for syphilis, infection with herpes simplex virus, gonorrhea, and (in North America) infection with Chlamydia trachomatis. The clinical history of the disease should be recorded and ulcers, buboes, and lymphadenitis mass described. Whenever possible, study participants also should be tested for HIV infection. Randomized, prospective, double-blind, active-control comparative clinical trials are preferred for evaluation of the safety and efficacy of new anti-infective drugs. Otherwise-healthy men and women should be enrolled in these studies. Patients with active syphilis or genital herpes should be excluded. Microbiological and clinical outcomes are paramount.
Anti-Infective Agents↗
Evaluation of new anti-infective drugs for the treatment of uncomplicated gonorrhea in adults and adolescents. Infectious Diseases Society of America and the Food and Drug Administration.
Gonorrhea is among the most common sexually transmitted diseases. Treatment for uncomplicated gonorrhea should be efficacious in > or = 95% of cases. Because patients with gonococcal infections often have other sexually transmitted diseases concurrently, individuals enrolled in clinical trials of therapy for gonorrhea should also be evaluated for infection with Chlamydia trachomatis and for syphilis. Testing for other pathogens should be considered in light of the clinical presentation. The presence of gonococcal infection is defined by a positive culture of a specimen obtained from an appropriate mucosal site. Patients enrolled in clinical trials should be otherwise-healthy adults who agree to return for follow-up assessment. These patients should be stratified by gender and anatomic site of infection. The preferred study design is a prospective, randomized, double-blind, active-control comparison. In some circumstances, however, historical controls may suffice. The study drug must have an efficacy rate of > or = 95% in genital and rectal infections. Microbiological eradication, demonstrated by negative cultures of samples from all potentially infected mucosal sites at follow-up, is the sole determinant of efficacy.
Adolescent↗
Evaluation of new anti-infective drugs for the treatment of sexually transmitted chlamydial infections and related clinical syndromes. Infectious Diseases Society of America and the Food and Drug Administration.
This guideline addresses clinical trials of new antimicrobial agents in the treatment of uncomplicated genital infections caused by Chlamydia trachomatis and of syndromes resembling chlamydial infections. The most common clinical manifestations of chlamydial infection are urethritis in men and mucopurulent cervicitis in women. However, many chlamydial infections are not associated with inflammatory symptoms or signs. Culture is the diagnostic standard for defining the presence of C. trachomatis, although nonculture tests may be used in screening patients for enrollment in clinical trials. Susceptibility testing for C. trachomatis is laborious and difficult to standardize; only a few clinical isolates need to be tested in vitro. Prospective, randomized, double-blind, active-control comparative studies are recommended. Eradication of C. trachomatis defines both microbiological success and overall cure for chlamydial infection, but clinical and nonmicrobiological laboratory criteria are paramount in assessing the therapeutic response in nonchlamydial urethritis or cervicitis.
Anti-Bacterial Agents↗
Evaluation of new anti-infective drugs for the treatment of syphilis. Infectious Diseases Society of America and the Food and Drug Administration.
Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.
Animals↗
Evaluation of new anti-infective drugs for the treatment of selected infections of the skin and skin structure. Infectious Diseases Society of America and the Food and Drug Administration.
No method for classifying infections of the skin and skin structure is uniformly accepted. Therefore, each protocol for the evaluation of new anti-infective drugs must include definitions of the skin and skin-structure infections to be treated. Clinical findings may suggest the etiology. Cultures should be performed by the best available technique. Because the yield of pathogens from sites of skin and skin-structure infection is often low, monitoring of the clinical response to therapy is paramount. Randomized, double-blind, active-control comparative studies are needed, and maintenance of blinding is recommended, even with a change in the route of administration of the study and/or control drugs. The period of follow-up should be defined for each type of infection.
Anti-Infective Agents↗
Evaluation of new anti-infective drugs for the treatment of osteomyelitis in adults. Infectious Diseases Society of America and the Food and Drug Administration.
Cases of osteomyelitis can be divided into four categories: acute hematogenous, vertebral, secondary to a contiguous focus of infection without vascular disease, and secondary to a contiguous focus of infection with vascular disease. Each category may be further divided into acute and chronic forms. Clinical symptoms persisting for > or = 10 days correlate roughly with the development of necrotic bone and chronic osteomyelitis. Patients enrolled in clinical trials should generally be > or = 12 years of age. Prior antimicrobial treatment does not exclude patients if the culture of a bone sample obtained at the time of enrollment yields pathogenic bacteria. Randomized, double-blind, active-control comparative studies are encouraged. Clinical outcome should be assessed during therapy and within 5-9 days, 4-6 weeks, and 11-13 months after completion of therapy. In the final assessment, clinical appraisal is paramount.
Adult↗
Evaluation of new anti-infective drugs for the treatment of acute hematogenous osteomyelitis in children. Infectious Diseases Society of America and the Food and Drug Administration.
Most children with acute hematogenous osteomyelitis have no preceding illness. Their early symptoms are pain and fever. A bacterial etiology is established in approximately 75% of cases by needle aspiration of the affected site or blood culture. Clinical trials should be limited to cases of bacterial origin. The antimicrobial agents studied should be active against Staphylococcus aureus and streptococci. If children < 5 years of age are included, the drug should also be active against beta-lactamase-negative and -positive strains of Haemophilus influenzae. Randomized, prospective, double-blind comparative studies are preferable to open, evaluator-blinded trials. Clinical outcome is appraised by physical signs and symptoms. A successful microbiological outcome consists of presumptive eradication. The final assessment should be made 1 year after completion of therapy.
Acute Disease↗
Evaluation of new anti-infective drugs for the treatment of infectious arthritis in adults. Infectious Diseases Society of America and the Food and Drug Administration.
This guideline describes clinical trials of new anti-infective drugs for the treatment of septic arthritis due to bacteria other than Neisseria gonorrhoeae in adults. Septic arthritis is associated with fever and with physical findings at the affected joint. Diagnosis is established by culture of synovial fluid. Treatment includes the administration of antimicrobial drugs and drainage of the joint by needle aspiration or surgery. Multicenter, randomized comparative clinical trials that are single-, double-, or evaluator-blinded should be performed. However, an open trial of a new antimicrobial agent with historical controls is acceptable. Patients should receive treatment for at least 2-3 weeks. After 5 days of antimicrobial therapy, synovial fluid should be sterile and clinical signs and symptoms should have diminished. Patients should be followed for 2-4 weeks after completion of therapy.
Adult↗
Evaluation of new anti-infective drugs for the treatment of acute suppurative arthritis in children. Infectious Diseases Society of America and the Food and Drug Administration.
Diagnostic criteria for bacterial suppurative arthritis include the demonstration of an inflammatory exudate by aspiration of synovial fluid and the isolation of bacteria from cultures of synovial fluid and/or blood. Clinical manifestations include joint effusion, swelling, tenderness, and pain, with or without redness of the overlying skin. Management consists of antimicrobial therapy, measures designed to relieve symptoms, surgical drainage of infected fluid, and physical therapy. Studies of new anti-infective therapy should be limited to cases of bacterial origin. Prospective, randomized, double-blind, or evaluator-blinded, active-control comparative clinical trials should be performed. Clinical response is characterized as success (cure), failure, or indeterminate outcome. The most common successful microbiological outcome is presumptive eradication. Follow-up should continue for 1 year before the final assessment.
Acute Disease↗
Evaluation of new anti-infective drugs for the treatment of infections of prosthetic hip joints. Infectious Diseases Society of America and the Food and Drug Administration.
Infections of a prosthetic hip are of three types: acute contiguous, chronic contiguous, and hematogenous. Acute contiguous infections result from contamination of the operative field at the time of surgery; clinical manifestations of infection become apparent within 6 months. Chronic contiguous infections are diagnosed 6-24 months postoperatively and are believed to be caused by intraoperative contamination. Hematogenous seeding of prosthetic joints accounts for infections that develop > or = 2 years after surgery. Fever and pain or dysfunction of the joint may be the only signs or symptoms of prosthetic hip joint infection. Definitive diagnosis is established by culture of a needle aspirate from the joint space or by intraoperative culture. Prospective, randomized, double-blind or evaluator-blinded, active-control comparative studies are preferable to open trials. Success rates 10-14 weeks after completion of a 4- to 6-week course of antimicrobial therapy should be > or = 90%.
Adult↗
Evaluation of new anti-infective drugs for the treatment of acute bacterial meningitis. Infectious Diseases Society of America and the Food and Drug Administration.
Predisposing conditions for acute bacterial meningitis include prematurity, young age, management in an intensive care setting, low socioeconomic background, and crowded living conditions. Clinical findings vary with age and may be nonspecific (altered feeding behavior) or specific (Kernig and Brudzinski signs). Examination and culture of cerebrospinal fluid (CSF) are essential for diagnosis. Antigen identification in CSF, serum, or urine by latex agglutination or other techniques can be useful in the identification of the pathogen. Randomized, controlled studies with a single-, double-, or evaluator-blinded design are encouraged. Among neonates, infants, and children, CSF should be examined again 24-36 hours after initiation of therapy. Outcomes should be judged by both clinical and microbiological criteria. Assessment of microbiological outcome is paramount.
Acute Disease↗
Evaluation of new anti-infective drugs for the treatment of cryptococcal meningitis. Infectious Diseases Society of America and the Food and Drug Administration.
Cryptococcus neoformans may infect persons with intact or compromised host defenses. Clinical manifestations generally correlate directly with the degree of immunosuppression. Treatment is prescribed on the basis of the severity of disease and the degree of immunosuppression. Cryptococcal meningitis is the most common clinical form of cryptococcal infection and the most amenable to study in clinical trials. The current standard of care for cryptococcal meningitis is therapy with amphotericin B. Despite clinical improvement and microbiological suppression of the organism at the completion of therapy, the microbiological outcome will be identified as presumptive persistence if treatment is continued. Patients should be observed for 1 year after completion of therapy before a final assessment is made.
Anti-Infective Agents↗
Evaluation of new anti-infective drugs for the treatment of viral encephalitis. Infectious Diseases Society of America and the Food and Drug Administration.
Viral encephalitis may develop subsequent to viremia, via neuronal spread, or by arthropod vector. Diagnosis often requires invasive studies such as lumbar puncture and brain biopsy. This guideline addresses herpes simplex, rabies, and arbovirus infections of the central nervous system. Clinical trials should be designed according to the availability of approved therapeutic agents. Study designs with an active control (herpesvirus), a placebo control (arbovirus), or no control (rabies virus) are recommended. Outcome should be assessed 4-6 weeks, 4-6 months, and 11-13 months after the completion of therapy. For newborns with encephalitis, outcome should be assessed yearly through the age of 5 years. Assessment of clinical outcome is paramount.
Anti-Infective Agents↗
Evaluation of new anti-infective drugs for the treatment of toxoplasma encephalitis. Infectious Diseases Society of America and the Food and Drug Administration.
Toxoplasma gondii is a protozoan that exists in three forms, all of which are potentially infectious for humans. After acute infection, cysts persist in the central nervous system and extraneural tissue. Human hosts with compromised immunity, particularly those with the acquired immunodeficiency syndrome, are vulnerable to reactivation and dissemination. The most common clinical expression of toxoplasma infection is encephalitis. The diagnosis is established by clinical presentation, computed tomography and/or magnetic resonance imaging, and detection of antibodies to T. gondii in serum of patients positive for human immunodeficiency virus. Brain biopsy may be performed. Protocols may be developed for the evaluation of new regimens for the treatment of acute encephalitis, the suppression of disease after treatment, or the prevention of reactivation before the onset of clinical disease. Assessment of clinical outcome is paramount.
Anti-Infective Agents↗