MinTAC: Tacrolimus Versus Prednisolone for the Treatment of Minimal Change Disease

• Sponsor: Imperial College Healthcare NHS Trust (Other)
• Overall Status: Completed
• CT.gov ID: NCT00982072
• Collaborator: (none)
• Enrollment: 52
• Location: 1
• Arms: 2
• Actual Duration (Months): 118.3
• Patients Per Site Per Month: 0.4

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
Minimal Change Disease	Drug: tacrolimus; Drug: prednisolone	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

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tacrolimus vs Prednisolone for the Treatment Minimal Change Disease
• Actual Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Oct 10, 2019
• Actual Study Completion Date: Oct 10, 2019

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: prograff

Outcome Measures

Primary Outcome Measures

1. 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

1. Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks [16 and 26 weeks]

2. Percentage of Patients Achieving Remission Who Then Relapse [2 years]

3. Number of Serious Adverse Events [3 years]

4. Change in Baseline Glomerular Filtration Rate [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

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)

• Study Protocol and Statistical Analysis Plan - Feb 2, 2013

More Information

Publications

None provided.

• Responsible Party: Imperial College Healthcare NHS Trust
• ClinicalTrials.gov Identifier: NCT00982072
• Other Study ID Numbers: 13HH1283; 2009-014292-52
• First Posted: Sep 22, 2009
• Last Update Posted: May 4, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College Healthcare NHS Trust: nephrotic minimal change tacrolimus prednisolone
• Additional relevant MeSH terms: Nephrosis, Lipoid; Prednisolone; Tacrolimus

Study Results

Participant Flow

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

1. Primary Outcome

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

2. Secondary Outcome

Title	Percentage of Patients Achieving Complete Remission From Nephrotic Syndrome at 16 and 26 Weeks
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%

3. Secondary Outcome

Title	Percentage of Patients Achieving Remission Who Then Relapse
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%

4. Secondary Outcome

Title	Number of Serious Adverse Events
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

5. Secondary Outcome

Title	Change in Baseline Glomerular Filtration Rate
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
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

[Not Specified]

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.