Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa study protocol for a randomized controlled trial. Study Design. A phase II open label randomized controlled clinical trial. Main Objectives. To assess the efficacy of the following treatments for primary VL at day 2. Liposomal amphotericin B and a 1. SSGthe combination of single dose Liposomal amphotericin B and a 1. Ancillary Files Stata' title='Ancillary Files Stata' />Even more Account Options. Sign in Search settings. Academic Careers. Salary offers are extended by Human Resources and will depend on available funding, candidates relevant experience and education, internal equity. SiteImages/9-SchoolImages/9-CMI/9-Stat351.png' alt='Ancillary Files Stata' title='Ancillary Files Stata' />Miltefosinea 2. Miltefosine. Setting. The areas of the two trial sites are endemic for VL. They are Dooka Hospital, Gedarif State, Sudan and Kimalel Hospital, Baringo district, Kenya. Addition of another Sudanese site will be considered. Data are brought to the Data Centre based at the studys Coordination Centre in Nairobi, Kenya. The trial is being conducted by the Leishmania East Africa Platform LEAP http www. Drugs for Neglected Diseases initiative http www. Outcome measures. SiBook CE 1. 0 Premessa package SiBook CE version 1. Copyright C 2012 Alessio Chiga. All rights reserved. GNUGPLv3. Primary outcome. The primary endpoint is initial cure, assessed at day 2. Sudan and bone marrow or spleen aspirate for Kenya. Figure 1. Consort Trial Diagram. Secondary outcomes. Final cure, defined as the percentage of patients cured at day 2. Adverse events and serious adverse events occurring in the three study arms up to day 6. Description of the pharmacodynamic properties of all the three arms. Description of the pharmacokinetic properties of Miltefosine alone and in combination with Liposomal amphotericin B. BackgroundThe rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public. Express Helpline Get answer of your question fast from real experts. The Ilford Manual Of Photography Pdf Tutorials on this page. Allocation. Randomization sequences were generated, stratified by site in pre determined block sizes by the Data Centre. Randomization codes have been concealed from investigators at the trial sites using sealed sequentially numbered, opaque envelopes. A copy of the randomization list is securely stored at the Data Centre. The envelopes are numbered sequentially externally. Inside each one there is a randomization sheet with the same sequential number as well as the treatment allocation. These randomization sheets are filed in the source documents which the monitor verifies at each site visit to confirm that only one envelope was opened for each patient to ensure integrity of the randomization process. Outpatient Mastectomy and Breast Reconstructive Surgery John Bian, PhD,1 Helen Krontiras, MD,2 and Jeroan Allison, MD3 1HSRD, Atlanta VA Medical Center, 1670. Number 0352. Policy. Aetna considers any of the following serum tumor markers for the stated indication medically necessary Prostatespecific antigen PSA for. Interventions. Liposomal amphotericin B is being given as a single dose on day 1 at a dose of 1. Miltefosine is being given orally at a dose of 2. Miltefosine is being given orally at a dose of 2. Liposomal amphotericin B 1. SSG is being given IVIM at a once daily dose of 2. Liposomal amphotericin B. Therefore the dose regimens is as follows. Liposomal amphotericin B one dose of 1. IV on day 1 followed by 1. SSG at 2. 0 mgkg body weight IVIM from days 2 1. Liposomal amphotericin B one dose of 1. IV on day 1 followed by 1. Monotherapy course of miltefosine at 2. All failure with compliance will be documented on the trial medication pages of the CRF. Screening. Inclusion criteria. Patients with clinical signs of VL fever for at least 2 weeks and splenomegaly and diagnosis confirmed by visualization of parasites in tissue samples on microscopy, aged between 7 and 6. HIV status. Exclusion criteria. Patients who have received any anti leishmanial drugs in the last 6 monthsrelapse cases, negative lymph nodebone marrow or spleen smears, severe protein and or caloric malnutrition, previous history of hypersensitivity reaction to SSG or Amphotericin B, suffering from concomitant severe infection such as TB or other serious underlying disease which would preclude evaluation of patients response to study medication, suffering from other conditions associated with splenomegaly such as schistosomiasis, previous history of cardiac arrhythmia or an abnormal ECG, female of child bearing age pregnant or lactating, haemoglobin lt 5 mgd. L, WBC lt 1 1. ALT and AST of more than three times the upper limit of the normal range, serum creatinine outside the normal range for age and gender, major surgical intervention within two weeks prior to enrolment. These tests are standardised but it is not feasible to standardise routine clinical laboratory assessments as different machines and reagents are being used. However both internal and external QC will be carried out at both sites on a regular basis and training offered to site staff at the beginning and during the trial to ensure that the data collected are reliable and comparable. HIV status and VCTAll patients are offered counselling and screening for HIV voluntary counselling and testing programme VCT. This is done at the same time as consent is obtained for inclusion in the trial. Patients who decline VCT or are found to be HIV positive are not eligible to participate in this trial but receive appropriate treatment, according to national treatment guidelines. Additionally, they are referred onwards for treatment, surveillance and follow up according to the national protocol for HIV positive patients. Consent. Standardised consent forms, adapted to the local context and translated into local languages and approved by ethics committees are being used. Signatures or thumbprints are obtained for consent, with witnesses in the latter case illiterate subjects for adults. In the case of children, the investigator gets their assent once permission of either the childs parent or guardian has been obtained. Patients who do not meet inclusion criteria or who do not give consent are offered free treatment outside the trial, according to national treatment guidelines. Analysis and sample size. Analysis of primary endpoint cure at day 2. The study is designed and will be analyzed according to group sequential methods, specifically the triangular test 1. Following the trials main objectives, the aim of the analysis is to efficiently identify a regimen that is a inadequate, so its development can be discontinued, or b adequate, so its development can proceed. In these terms, the highest efficacy i. The null and alternative hypotheses are H0 p p. H1 p pa respectively. The triangular stopping boundary, as shown in Figure 2, was defined following Ranque et al 1. With both type I and type II error rates set at 5 power 9. The actual sample size may be less than this, depending on when the actual percentage of patients cured leads to a boundary being crossed. The boundaries were calculated using custom written functions in the R software 1. Ranque et al 1. 0. Figure 2. Triangular region for study arms. Showing the boundaries for analyzing the sequential trial using the Triangular test with the following parameters p. The vertical line at n 3. PK component of the trial, a minimum of 3. Each analysis consists of calculating the quantities V proportional to current sample size and Z number of observed minus expected treatment successes and plotting them on Figure 2. Hence, for each arm, a line from the origin is plotted over time. Recruitment in an arm will be stopped when this line crosses either boundary of the triangular region. Crossing the lower or upper boundary means concluding inadequacy or adequacy, respectively. Since the three arms will be assessed separately, it is possible that one of them may be stopped prior to others. The above procedure is subject to a constraint imposed for the PK component of the trial, which requires at least 3. Therefore, if the upper boundary is crossed at n 1. However, if the lower boundary is crossed indicating inadequate efficacy at n 1. Crossing a boundary of the region implies that the percentage of patients cured is either greater than 9. The maximum likelihood estimate of the efficacy, i. To take this into account, the analysis will follow Bellissant et al 1. First, the sample quantity C will be calculated as Open image in new window, where Vis the terminal value of V from the data sample, and the aparameter is the log odds ratio logep1 p. Then, the tables in Whiteheads Appendix A 1. The latter are provided in terms of factors by which to multiply a. Finally, these three values of i.