- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00203281
Study to Evaluate the Amount of Medications That May be Removed From the Body During Plasmapheresis
Pharmacokinetic Evaluation of Plasmapheresis in Cross Match Positive or ABO Incompatible Kidney Allograft Recipients
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
Kidney transplantation has emerged as a desired treatment of choice for patients with end stage renal disease. Although transplantation has become increasingly successful, there continues to be risks associated with it. Prior to performing a kidney transplant patients are cross-matched (a test to determine whether or not they have preformed antibodies to the donor). Preformed antibodies result from a previous pregnancy, blood or platelet transfusion or prior transplant. Performing a transplant in patients who have preformed antibodies against the donor generally results in hyperacute rejection (when the immune system attacks the new kidney). This hyperacute rejection usually results in kidney loss in a very high percentage of patients. Due to these consequences, pre-transplant cross-matching has emerged as a standard of care. Although hyperacute kidney loss has now been avoided, a large population of highly sensitized patients that has little hope of receiving a transplant has been identified.
A number of groups have studied methods to lower specific antibody levels in a variety of clinical settings. The two primary methods used today in transplantation are plasmapheresis (the separation of plasma from cells, and the removal of solutes, immune globulins, and medications) and administration of immune globulin therapy. Employing either of these techniques individually or jointly has substantially reduced acute rejection and improved kidney survival in these highly sensitized patients. The immune globulin treatments that have been studied have included large variations in dosage as well as differences in immune globulin products. The results from these small studies have not identified one therapy, product or dosage that could be considered standard of care.
The kidney transplant work-up also consists of matching ABO blood group between donor and recipient. Transplantation against the recipient blood group has resulted in very poor outcomes due to antibody mediated rejection (when the immune system attacks the kidney). However, due to the shortage of organs available for transplantation, the increasing number of patients awaiting a transplant and the favorable outcomes with live donor transplant, some transplant programs have developed protocols for transplanting against the recipient ABO blood group. These protocols are centered around plasmapheresis and treatment with immune globulin. As with the positive cross-match patients stated earlier, the standard of care has yet to be identified.
Dr. Lloyd Ratner, currently at Columbia University and former Chief of Transplant at Thomas Jefferson University Hospital and his former colleagues at Johns Hopkins University have studied the use of plasmapheresis in combination with Cytomegalovirus Immune Globulin Intravenous (CytoGam) to reverse a positive cross match and to transplant organs against ABO incompatible blood groups. This has enabled over 20 kidney transplants to be performed with patient and graft survival at one year being very similar to our traditional cross match negative and ABO compatible patients. These results are generally considered outstanding given the fact that antibody mediated rejection historically had a 75 to 100% incidence of graft loss.
The treatment protocol that is used consists of plasmapheresis treatments alternating with CytoGam infusions every other day for 3 to 9 treatments prior to transplantation and another 1-5 treatments after transplant. Plasmapheresis is increasingly performed to treat various infectious, immunological, metabolic and inherited diseases. In this procedure, plasma and cellular components of blood are separated and solutes in plasma, including drugs may be removed. Generally, a volume of 1 to 1.5 times the plasma volume is removed and replaced with an equivalent volume of crystalloid or colloid. The procedure removes solutes or drugs from the blood compartment and the tissue stores remain unaffected except for re-equilibration with decreasing plasma concentrations. After each plasmapheresis treatment patients receive an infusion of CytoGam which is used to "inactivate" the remaining antibody. However, it is not known to what extent subsequent treatments of plasmapheresis remove CytoGam that patients received only hours or days prior.
During the treatment phase with plasmapheresis patients also receive a number of other medications such as immunosuppressants for the prevention and treatment of graft rejection, antibiotics for prevention and treatment of infection and various other medications for related illnesses. The effects that plasmapheresis may have on removal of these medications is not known for many of these agents. This information would be helpful for the potential need to re-dose or give supplemental doses of medications. This is extremely important for the immunosuppressant medications since under-dosing of these agents may result in serious negative outcomes. Due to these many unknown aspects it would be useful to know the extent of drug removal during plasmapheresis treatments. This would enable more precise dosing and ultimately better patient care.
Tipo di studio
Contatti e Sedi
Luoghi di studio
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New York
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New York, New York, Stati Uniti, 10032
- Columbia University
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19107
- Thomas Jefferson University Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
Descrizione
Inclusion Criteria:
- Patient is a male or female.
- Age of 18-75.
- Patient must have the ability to provide informed consent.
- Positive cross-match with intended donor and/or ABO incompatible with intended donor.
Exclusion Criteria:
- Patients under the age of 18 or over the age of 75.
- Women that are currently pregnant.
- Patient has a history of any illness that, in the opinion of the investigator(s), might confound the results of the study or pose additional risk to the patient.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
Collaboratori e investigatori
Investigatori
- Investigatore principale: Mark Chaballa, PharmD, Thomas Jefferson University
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Anticipato)
Completamento dello studio (Anticipato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Inibitori enzimatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti antibatterici
- Antibiotici, Antineoplastici
- Agenti antitubercolari
- Antibiotici, Antitubercolari
- Inibitori della calcineurina
- Anticorpi
- Immunoglobuline
- Immunoglobuline, per via endovenosa
- Tacrolimo
- gamma-globuline
- Immunoglobulina Rho(D).
- Acido micofenolico
- Daclizumab
Altri numeri di identificazione dello studio
- 03U.86
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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