Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children

• Sponsor: Seoul National University Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01162005
• Collaborator: Chong Kun Dang Pharmaceutical (Industry)
• Enrollment: 77
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

To determine the efficacy of tacrolimus in the management of NS(nephrotic syndrome) , the investigators designed this prospective study. The investigators will enroll 100 children with NS(frequent relapse steroid dependent NS, steroid resistance NS) who will be treated with tacrolimus (0.1-0.2 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 5 and 10 ng/ml) for 12 months in combination with low-dose steroids. Other therapies will be included angiotensin-converting enzyme inhibitors, antihypertensive drugs, multivitamins and lipid-lowering agents.

Follow-up is every second week for the first 4 weeks, then monthly. After initiation of tacrolimus therapy, blood was drawn each visit to determine tacrolimus trough levels.

Condition or Disease	Intervention/Treatment	Phase
Nephrotic Syndrome	Drug: Tacrolimus	Phase 4

Detailed Description

Subsequently , monthly measurements were made until stable levels of tacrolimus were achieved. Urine was analyzed for proteinuria at each visit. Serum creatinine, glucose, albumin and alanine aminotransferase were measured and complete blood counts were obtained at each visit during the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tacrolimus Tacrobell	Drug: Tacrolimus; dosage : 0.1-0.2 mg/kg/day divided two target trough level : 5 - 10 ng/mL Total duration (tacrolimus) : 1 year; Other Names: Trcrobell

Outcome Measures

Primary Outcome Measures

1. Remission Rate [12-month treatment period]

   Complete remission at 12 months Per KDIGO clinical practice guideline for glomerulonephritis (2012): Complete remission (CR), urine protein creatinine ratio below 200mg/g (20mg/mmol) or 1+ of protein on urine dipstick for 3 consecutative days

Secondary Outcome Measures

1. Duration of Remission [12-month treatment period]

   Mean duration of remission

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Frequent relapse nephrotic syndrome

• steroid resistance nephrotic syndrome

Exclusion Criteria:

• secondary nephrotic syndrome

• estimated glomerular filtration rate < 60 mL/min/1.73m2

• with active hepatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of	110-744

Sponsors and Collaborators

• Seoul National University Hospital
• Chong Kun Dang Pharmaceutical

Investigators

• Study Chair: ILSOO Ha, MD, PhD, Seoul National Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Il Soo Ha, Study chair, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT01162005
• Other Study ID Numbers: INS-Tacrobell; INS-Tacrobell-Pediatrics
• First Posted: Jul 14, 2010
• Last Update Posted: Feb 7, 2019
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Il Soo Ha, Study chair, Seoul National University Hospital: Primary Nephrotic syndrome
• Additional relevant MeSH terms: Nephrotic Syndrome; Nephrosis; Syndrome; Tacrolimus

Study Results

Participant Flow

Recruitment Details	From July 2010 to August 2013, children with refractory NS were enrolled. It was conducted at three centers in Korea after obtainment of informed consent. ( Seoul National University Children's Hospital, Samsung Medical Center, Asan Medical Center Children's Hospital)

Arm/Group Title	SDNS/FRNS Group	SRNS Group
Arm/Group Description	Indicative of two or more relapses during tapering or within 14 days of stopping steroid therapy or more than four relapses within one year or at least two within six months SDNS: steroid-dependent nephrotic syndrome; FRNS: frequent-relapsing nephrotic syndrome;	Absence of remission after four weeks of steroid therapy SRNS: steroid-resistant nephrotic syndrome
Period Title: Overall Study
STARTED	44	33
COMPLETED	44	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	SDNS/FRNS Group	SRNS Group	Total
Arm/Group Description	SDNS: steroid dependent nephrotic syndrome FRNS: frequent relapsing nephrotic syndrome Indicative of two or more relapses during tapering or within 14 days of stopping steroid therapy or more than four relapses within one year or at least two within six months	SRNS: steroid resistant nephrotic syndrome Absence of remission after four weeks of steroid therapy.	Total of all reporting groups
Overall Participants	44	33	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.4 (4.2)	7.9 (4.2)	9.9 (4.2)
Sex: Female, Male (Count of Participants)
Female	9 20.5%	14 42.4%	23 29.9%
Male	35 79.5%	19 57.6%	54 70.1%

Outcome Measures

1. Primary Outcome

Title	Remission Rate
Description	Complete remission at 12 months Per KDIGO clinical practice guideline for glomerulonephritis (2012): Complete remission (CR), urine protein creatinine ratio below 200mg/g (20mg/mmol) or 1+ of protein on urine dipstick for 3 consecutative days
Time Frame	12-month treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SDNS/FRNS	SRNS
Arm/Group Description	Indicative of two or more relapses during tapering or within 14 days of stopping steroid therapy or more than four relapses within one year or at least two within six months	Absence of remission after four weeks of steroid therapy
Measure Participants	44	33
Count of Participants [Participants]	34 77.3%	13 39.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SDNS/FRNS, SRNS
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Duration of Remission
Description	Mean duration of remission
Time Frame	12-month treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SDNS/FRNS Group	SRNS Group
Arm/Group Description	Indicative of two or more relapses during tapering or within 14 days of stopping steroid therapy or more than four relapses within one year or at least two within six months	Absence of remission after four weeks of steroid therapy
Measure Participants	44	33
Mean (Standard Deviation) [months]	4.6 (2.9)	4.0 (3.2)

Adverse Events

Time Frame	12 months
Arm/Group Title	SDNS/FRNS Group		SRNS Group
Arm/Group Description	Indicative of two or more relapses during tapering or within 14 days of stopping steroid therapy or more than four relapses within one year or at least two within six months		Absence of remission after four weeks of steroid therapy
All Cause Mortality
	SDNS/FRNS Group		SRNS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/33 (0%)
Serious Adverse Events
	SDNS/FRNS Group		SRNS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		4/33 (12.1%)
Renal and urinary disorders
Decreased renal function	0/44 (0%)	0	4/33 (12.1%)	4
Other (Not Including Serious) Adverse Events
	SDNS/FRNS Group		SRNS Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/44 (6.8%)		16/33 (48.5%)
Blood and lymphatic system disorders
Transient glycosuria	3/44 (6.8%)	3	8/33 (24.2%)	8
Transient hyperglycemia	0/44 (0%)	0	1/33 (3%)	1
Gastrointestinal disorders
Gastrointestinal trouble	0/44 (0%)	0	1/33 (3%)	1
Nervous system disorders
Headache	0/44 (0%)	0	2/33 (6.1%)	2
Dizziness	0/44 (0%)	0	1/33 (3%)	1
Tremor	0/44 (0%)	0	2/33 (6.1%)	2
Skin and subcutaneous tissue disorders
Itching sensation	0/44 (0%)	0	1/33 (3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.