Minimal Change Disease
Conditions
Keywords
nephrotic minimal change tacrolimus prednisolone
Brief summary
The purpose of this study is to compare the effectiveness of tacrolimus (prograf) versus prednisolone for the treatment of nephrotic syndrome secondary to minimal change disease.
Detailed description
Minimal change disease is a common cause of nephrotic syndrome in adults. Standard treatment is with high dose steroids which is often effective in controlling the nephrotic syndrome but has a high morbidity due to the side effects of the steroids. There is also a high relapse rate,therefore many patients require long term steroid therapy to control their disease which has significant morbidity and mortality. Some patients are or also become steroid resistant. There are studies showing the effectiveness of alkylating agents such as cyclophosphamide but the use of these drugs is limited by their toxicity, including increased rates of infection, cancers and infertility. Tacrolimus (prograf) is a T-cell specific calcineurin inhibitor that shares similar immunosuppressive actions with cyclosporine A.In other glomerular diseases such as focal segmental glomerulosclerosis and membranous glomerulonephritis, prograf has been shown to be a very effective treatment for proteinuria. This may be due to the immunomodulatory effects on the underlying disease, but there may also be a direct effect of tacrolimus (prograf) on the podocyte, stabilising the actin cytoskeleton and therefore decreasing protein leak.Therefore tacrolimus (prograf) is likely to be effective in reducing proteinuria in minimal change disease.It has also been shown to have a good side effect profile when used to allow the avoidance of steroids in transplantation.This study aims to prospectively study if tacrolimus (prograf) is effective as treatment for minimal change disease compared with standard therapy with steroids, and whether it has advantages in terms of side effect profile and prevention of relapse.
Interventions
DRUGtacrolimus
tacrolimus0.05mg/kg bd (levels 6-12ng/ml)
DRUGprednisolone
Prednisolone 1mg/kg maximum 60mg od
Sponsors
Imperial College Healthcare NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with nephrotic syndrome (hypoalbuminaemia and protein creatinine ratio (PCR) \> 100units), secondary to minimal change disease. * Age over 18.
Exclusion criteria
* Hepatitis B, hepatitis C or HIV infection. * Untreated infection. * Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception. * Patients who have been treated with immunosuppression over the last 18 months. * Patients who have had more than 3 relapses of nephrotic syndrome within 5 years. * Any condition judged by the investigator that would cause the study to be detrimental to the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks | 8 weeks | normalisation of serum albumin and urine PCR \<50 units |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Patients Achieving Remission Who Then Relapse | 2 years |
| Number of Serious Adverse Events | 3 years |
| Change in Baseline Glomerular Filtration Rate | 3 years |
| Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks | 16 and 26 weeks |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prednisolone prednisolone tablets
prednisolone: Prednisolone 1mg/kg maximum 60mg od | 25 |
| Tacrolimus tacrolimus tablets
tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) | 27 |
| Total | 52 |
Baseline characteristics
| Characteristic | Tacrolimus | Total | Prednisolone |
|---|---|---|---|
| Age, Customized 18 years and over | 27 Participants | 52 Participants | 25 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 27 participants | 52 participants | 25 participants |
| Sex: Female, Male Female | 15 Participants | 25 Participants | 10 Participants |
| Sex: Female, Male Male | 12 Participants | 27 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 27 |
| other Total, other adverse events | 18 / 25 | 20 / 27 |
| serious Total, serious adverse events | 4 / 25 | 3 / 27 |
Outcome results
Primary
Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks
normalisation of serum albumin and urine PCR \<50 units
Time frame: 8 weeks
Population: Patients at 8 weeks of therapy- on intention to treat basis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prednisolone | Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks | 21 Participants |
| Tacrolimus | Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks | 17 Participants |
p-value: 0.12Fisher Exact
Secondary
Change in Baseline Glomerular Filtration Rate
Time frame: 3 years
Population: data not collected
Secondary
Number of Serious Adverse Events
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisolone | Number of Serious Adverse Events | 4 serious adverse events |
| Tacrolimus | Number of Serious Adverse Events | 3 serious adverse events |
Secondary
Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks
Time frame: 16 and 26 weeks
Population: Patients on intention to treat basis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prednisolone | Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks | 16 weeks | 23 Participants |
| Prednisolone | Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks | 26 weeks | 23 Participants |
| Tacrolimus | Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks | 16 weeks | 19 Participants |
| Tacrolimus | Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks | 26 weeks | 22 Participants |
Secondary
Percentage of Patients Achieving Remission Who Then Relapse
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Prednisolone | Percentage of Patients Achieving Remission Who Then Relapse | 17 Participants |
| Tacrolimus | Percentage of Patients Achieving Remission Who Then Relapse | 16 Participants |