A Prospective Study on the Tolerability and Efficacy of the de Novo Use of Myfortic in Liver Transplant Recipients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil
研究概览
简要总结
The objective of this study is to compare the safety and efficacy of Myfortic with CellCept in liver transplant patients. Myfortic and CellCept are both immunosuppressive (anti-rejection) drugs. CellCept is commonly used after liver transplantation but gastrointestinal (GI) side effects are very common, sometimes necessitating in its discontinuation. Myfortic is a new drug similar to CellCept, except it is enteric-coated. Our hypothesis is that Myfortic has less GI side effects than CellCept and also has comparable effectiveness to CellCept.
详细描述
This is a prospective, randomized, double-blinded, single center, safety and efficacy study comparing Myfortic with CellCept used after liver transplantation. Patients with biopsy-proven acute cellular rejection, renal insufficiency (i.e. acute or chronic renal failure requiring hemodialysis or patients with creatinine clearance < 50 ml/min), or calcineurin inhibitor-induced neurotoxicity (defined as the presence of neurologic symptoms such as tremors, altered mental status, seizures, etc) will be randomized to start on either Myfortic (720 mg po bid) or CellCept (1 gm po bid). In those patients with calcineurin-induced neurotoxicity or nephrotoxicity, tacrolimus or cyclosporine doses will also be reduced to maintain serum trough levels of 4-8 mg/dl or 100-200 mg/dl, respectively.
Comparison: Thirty patients will be enrolled and randomized in this two-armed, double-blinded study- half of the patients will receive Myfortic and the other half, CellCept.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ALL patients will be adult liver transplant recipients, males or females, 18-80 years of age.
- •Patients must be 30 to 180 days (1 to 6 months) post-transplant to be eligible.
- •Patients currently receiving tacrolimus or cyclosporine with or without corticosteroids as part of their immunosuppressive regimen.
- •Patients with renal insufficiency (history of renal insufficiency or renal failure in the past, patients on hemodialysis, patients with a rising creatinine post-transplant).
- •Patients with biopsy-proven acute cellular rejection (mild, moderate, or severe based on Rejection Activity Index (RAI) as graded by pathologists at UPMC) or repeated bouts of rejection (greater than 2 episodes within a 30 day period).
- •Patients with tacrolimus- or cyclosporine-induced neurotoxicity.
- •Females of childbearing potential must have a negative serum pregnancy test prior to the inclusion period.
排除标准
- •Multi-organ transplant patients.
- •HIV positive patients.
- •Living-related liver transplant recipients
- •Pregnant patients and nursing mothers.
- •Patients with a history of extra-hepatic malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin.
- •Patients with thrombocytopenia (<50,000/mm3), with an absolute neutrophil count of <1,000/mm3 and/or leukocytopenia (<2,000/mm3), and/or hemoglobin <7.0 g/dL prior to enrollment.
- •Presence of clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus.
- •Evidence of drug and/or alcohol abuse.
- •Decisionally impaired subjects who are not medically or mentally capable of providing consent themselves
研究组 & 干预措施
Myfortic Group
Subjects in the Myfortic arm will receive Myfortic 360mg or 720 mg BID for 90 days
干预措施: Myfortic (Drug)
CellCept Group
Subjects in the CellCept arm will receive CellCept 500mg or 1000mg BID for 90 days
干预措施: CellCept (Drug)
结局指标
主要结局
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The total GSRS range of scores is 15 to 105 with higher scores meaning the worst of symptoms.
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Abdominal Pain Subscale)
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The abdominal Pain subscale range is 3 to 21 with higher scores means worst symptoms
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Reflux Subscale)
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. Reflux subscale range is 2 to 14 with higher scores means worst symptoms
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Indigestion Subscale)
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The Indigestion subscale range is 4 to 28 with higher scores means worst symptoms
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Diarrhea Subscale)
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The Diarrhea subscale range is 3 to 21 with higher scores means worst symptoms
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Constipation Subscale)
时间窗: screening, 2, 6 and 12 weeks
The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation). The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. Constipation subscale range is 3 to 21 with higher scores means worst symptoms
Number of Participants With Bone Marrow Suppression
时间窗: 12 weeks
Number of participants with: Thrombocytopenia (\<50,000 mm3), Leukopenia (\< 2000 mm3), absolute neutrophils count ( \<1000 mm3) or hemoglobin ( \< 7.0 g/dL)
Incidence of Cytomegalovirus Infection or Disease During the Study Period
时间窗: 12 weeks
number of participants
次要结局
- Drug Discontinuation Due to Side Effects(12 weeks)
- Number of Participants With Clinically Significant Decrease in Serum Creatinine From Baseline Through Week 12(12 weeks)
- Number of Participants With Neurotoxicity(12 weeks)
研究者
Roberto Lopez, MD
Assistant Professor of Surgery
University of Pittsburgh