Gastrointestinal Symptoms, Heart Transplantation
Conditions
Keywords
Heart Transplant, gastrointestinal, Cellcept, Myfortic, GI, GI symptoms with Mycophenolate Mofetil post heart transplant
Brief summary
Mycophenolate sodium (Myfortic®) is a newly developed enteric-coated tablet version of mycophenolate mofetil (Cellcept®) which is currently used as therapy for the prevention of transplant rejection. Myfortic® was developed to improve the gastrointestinal tolerability of Cellcept®. The new enteric-coated, Myfortic® is presently FDA approved for the prevention of acute kidney rejection only. There is no clinical data of its use in heart transplant patients.
Detailed description
This is an open-labeled, prospective, non-randomized pilot-phase study of the enteric-coated, Myfortic® versus the non enteric-coated, Cellcept® in patients who are within 5 years of having undergone heart transplant surgery who are currently taking Cellcept®. After the initial screening, 20 patients who fulfill the inclusion criteria and report symptoms of gastrointestinal side-effects while taking Cellcept will be switched to Myfortic. All 20 patients will be followed closely over a period of 6 months following enrollment. Concomitant immunosuppressive therapy will continue in all patients per standard treatment protocol.
Interventions
1440mg/day (720mg by mouth, twice a day)
Sponsors
Novartis Pharmaceuticals
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients of either sex aged 18 and above who have undergone successful orthotopic heart transplant surgery. 2. Patients who are currently taking Cellcept® and experiencing gastrointestinal side-effects from this standard therapy. 3. Individuals on Cellcept® with total dosage of 2 mg a day or less would be eligible to participate. 4. Patients who are able to give written informed consent.
Exclusion criteria
1. Patients with an absolute neutrophil count \<1500 cells/mm3, and/or leukocytopenia (\<2500 cells/mm3), thrombocytopenia (\<75,000 cells/mm3) and significant anemia (hemoglobin \< 6g/dl) at the time of potential enrollment. 2. Women of childbearing potential not using the contraception method(s), as well as women who are breastfeeding. 3. Known sensitivity to the study drug or class of the study drug. 4. Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study. 5. Use of any other investigational agent in the last 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GI Tolerability as Measured by GSRS | Baseline and 6 months | Side-effects using the GSRS (Gastrointestinal Symptoms Rating Scale) GSRS has 15 items, each rated on a 7-point scale from 1 (no discomfort) to 7 (very severe discomfort). GSRS total minimum value is 15; maximum value is 105. Higher scores represent greater discomfort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Biopsy Proven Acute Rejection, Graft Loss and Death Due to Rejection. | 6 months | Number of biopsy proven acute rejection, graft loss, and death due to rejection. Number of rejection episodes where rejection is defined as Grade 1B or higher on myocardial biopsy as measured by the 1990 Grading System of the International Society of Heart and Lung Transplantation for Acute Cellular Rejection. Grading system has: * grade 0 (no acute rejection) * grade 1A (Focal, mild acute rejection) * grade 1B (Diffuse, mild acute rejection) * grade 2 (Focal, moderate acute rejection) * grade 3A (multifocal moderate rejection) * grade 3B (Diffuse, borderline severe acute rejection) * grade 4 (Severe acute rejection). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enteric-coated Mycophenolate Sodium (Myfortic) 1440mg/day (720mg by mouth, twice a day) of enteric-coated Mycophenolate Sodium (Myfortic) for 6 months | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Enteric-coated Mycophenolate Sodium (Myfortic) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 11 |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 8 / 11 |
Outcome results
Primary
GI Tolerability as Measured by GSRS
Side-effects using the GSRS (Gastrointestinal Symptoms Rating Scale) GSRS has 15 items, each rated on a 7-point scale from 1 (no discomfort) to 7 (very severe discomfort). GSRS total minimum value is 15; maximum value is 105. Higher scores represent greater discomfort.
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enteric-coated Mycophenolate Sodium (Myfortic) | GI Tolerability as Measured by GSRS | GSRS at baseline | 55.67 score on a scale | Standard Deviation 15.49 |
| Enteric-coated Mycophenolate Sodium (Myfortic) | GI Tolerability as Measured by GSRS | GSRS at 6 months | 34.17 score on a scale | Standard Deviation 19.47 |
Secondary
Number of Biopsy Proven Acute Rejection, Graft Loss and Death Due to Rejection.
Number of biopsy proven acute rejection, graft loss, and death due to rejection. Number of rejection episodes where rejection is defined as Grade 1B or higher on myocardial biopsy as measured by the 1990 Grading System of the International Society of Heart and Lung Transplantation for Acute Cellular Rejection. Grading system has: * grade 0 (no acute rejection) * grade 1A (Focal, mild acute rejection) * grade 1B (Diffuse, mild acute rejection) * grade 2 (Focal, moderate acute rejection) * grade 3A (multifocal moderate rejection) * grade 3B (Diffuse, borderline severe acute rejection) * grade 4 (Severe acute rejection).
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Enteric-coated Mycophenolate Sodium (Myfortic) | Number of Biopsy Proven Acute Rejection, Graft Loss and Death Due to Rejection. | No rejection (Grade 0 or 1A) | 20 myocardial biopsies |
| Enteric-coated Mycophenolate Sodium (Myfortic) | Number of Biopsy Proven Acute Rejection, Graft Loss and Death Due to Rejection. | Rejection (Grade 1B or higher) | 0 myocardial biopsies |
| Enteric-coated Mycophenolate Sodium (Myfortic) | Number of Biopsy Proven Acute Rejection, Graft Loss and Death Due to Rejection. | Death due to rejection | 0 myocardial biopsies |