MinTAC: Tacrolimus Versus Prednisolone for the Treatment of Minimal Change Disease
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: prednisolone prednisolone tablets |
Drug: prednisolone
Prednisolone 1mg/kg maximum 60mg od
|
Experimental: tacrolimus tacrolimus tablets |
Drug: tacrolimus
tacrolimus0.05mg/kg bd (levels 6-12ng/ml)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks [8 weeks]
normalisation of serum albumin and urine PCR <50 units
Secondary Outcome Measures
- Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks [16 and 26 weeks]
- 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]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Hammersmith Hospital | London | United Kingdom | W12 OHS |
Sponsors and Collaborators
- Imperial College Healthcare NHS Trust
Investigators
- Study Chair: Megan Griffith, MBChBPhDFRCP, Imperial College NHS Trust
- Principal Investigator: Tom Cairns, MBBSMRCP, Imperial College NHS Trust
Study Documents (Full-Text)
More Information
Publications
None provided.- 13HH1283
- 2009-014292-52
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Period Title: Overall Study | ||
STARTED | 25 | 27 |
COMPLETED | 25 | 25 |
NOT COMPLETED | 0 | 2 |
Baseline Characteristics
Arm/Group Title | Prednisolone | Tacrolimus | Total |
---|---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) | Total of all reporting groups |
Overall Participants | 25 | 27 | 52 |
Age, Customized (Count of Participants) | |||
18 years and over |
25
100%
|
27
100%
|
52
100%
|
Sex: Female, Male (Count of Participants) | |||
Female |
10
40%
|
15
55.6%
|
25
48.1%
|
Male |
15
60%
|
12
44.4%
|
27
51.9%
|
Race and Ethnicity Not Collected (Count of Participants) | |||
Count of Participants [Participants] |
0
0%
|
||
Region of Enrollment (participants) [Number] | |||
United Kingdom |
25
100%
|
27
100%
|
52
100%
|
Outcome Measures
Title | Percentage of Participants Achieving Complete Remission From Nephrotic Syndrome at 8 Weeks |
---|---|
Description | normalisation of serum albumin and urine PCR <50 units |
Time Frame | 8 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Patients at 8 weeks of therapy- on intention to treat basis |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Measure Participants | 25 | 27 |
Count of Participants [Participants] |
21
84%
|
17
63%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Prednisolone, Tacrolimus |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.12 |
Comments | ||
Method | Fisher Exact | |
Comments |
Title | Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks |
---|---|
Description | |
Time Frame | 16 and 26 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Patients on intention to treat basis |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Measure Participants | 25 | 27 |
16 weeks |
23
92%
|
19
70.4%
|
26 weeks |
23
92%
|
22
81.5%
|
Title | Percentage of Patients Achieving Remission Who Then Relapse |
---|---|
Description | |
Time Frame | 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Measure Participants | 23 | 22 |
Count of Participants [Participants] |
17
68%
|
16
59.3%
|
Title | Number of Serious Adverse Events |
---|---|
Description | |
Time Frame | 3 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Measure Participants | 25 | 27 |
Number [serious adverse events] |
4
|
3
|
Title | Change in Baseline Glomerular Filtration Rate |
---|---|
Description | |
Time Frame | 3 years |
Outcome Measure Data
Analysis Population Description |
---|
data not collected |
Arm/Group Title | Prednisolone | Tacrolimus |
---|---|---|
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) |
Measure Participants | 0 | 0 |
Adverse Events
Time Frame | Up to 3 years | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Prednisolone | Tacrolimus | ||
Arm/Group Description | prednisolone tablets prednisolone: Prednisolone 1mg/kg maximum 60mg od | tacrolimus tablets tacrolimus: tacrolimus0.05mg/kg bd (levels 6-12ng/ml) | ||
All Cause Mortality |
||||
Prednisolone | Tacrolimus | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/25 (0%) | 0/27 (0%) | ||
Serious Adverse Events |
||||
Prednisolone | Tacrolimus | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/25 (16%) | 3/27 (11.1%) | ||
Cardiac disorders | ||||
hypertension | 0/25 (0%) | 0 | 1/27 (3.7%) | 1 |
Gastrointestinal disorders | ||||
diverticualr disease | 1/25 (4%) | 1 | 0/27 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
fracture radius | 1/25 (4%) | 1 | 0/27 (0%) | 0 |
Nervous system disorders | ||||
headache | 1/25 (4%) | 1 | 0/27 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||
respiratory infection | 1/25 (4%) | 1 | 1/27 (3.7%) | 1 |
Skin and subcutaneous tissue disorders | ||||
rash and diarhoaea | 0/25 (0%) | 0 | 1/27 (3.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Prednisolone | Tacrolimus | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 18/25 (72%) | 20/27 (74.1%) | ||
General disorders | ||||
various non serious | 18/25 (72%) | 18 | 20/27 (74.1%) | 20 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr Megan Griffith |
---|---|
Organization | Imperial College NHS Trust |
Phone | 02033137309 |
m.e.griffith@imperial.ac.uk |
- 13HH1283
- 2009-014292-52