To Compare the Efficacy and Safety of FK506 vs IVC in the Treatment of Class III-IV LN - Full Text View

Sponsors and Collaborators:	Nanjing University School of Medicine Sun Yat-sen University
Information provided by:	Nanjing University School of Medicine
ClinicalTrials.gov Identifier:	NCT00302549

Purpose

To compare the efficacy of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN.
To compare the safety and tolerability of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN.
To explore the dosing of FK506 and its effective range of blood concentration.

Condition	Intervention
Lupus Nephritis	Drug: FK506

Drug Information available for: Cyclophosphamide Tacrolimus Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	To Compare the Efficacy and Safety of FK506 vs IVC in the Treatment of Class

Further study details as provided by Nanjing University School of Medicine:

Primary Outcome Measures:

To compare the efficacy of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To compare the safety and tolerability of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN and to explore the dosing of FK506 and its effective range of blood concentration. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment:	61
Study Start Date:	May 2004
Study Completion Date:	February 2006
Primary Completion Date:	May 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Active Comparator CTX	Drug: FK506 FK506,0.1mg/kg/d

Detailed Description:

Corticosteroid combined with cytotoxic drugs has been regarded as the conventional therapy for Class IV Lupus Nephritis (LN), because of its efficacy in improving patients' long term survival. However, this treatment fails in some patients, especially those who present with significant vascular lesion. In addition, cyclophosphamide (CTX) has severe side effects with a high incidence of marrow inhibition and infection.FK506 (Tacrolimus) is a new calcineurin inhibitor. Similar to Cyclosporine (CsA), it inhibits the production of IL-2 and activation of T cells. Furthermore, it has an added value of inhibiting the production of IL-10 from Th2 cells, thus reducing the production of auto antibodies from B cells.It also exerts its specific immunosuppressive effects through CsA-insensitive pathway. FK506 could inhibit not only the activation of naive T cells but also the activation and proliferation of primed T cells.FK506 is 10 -100 times more powerful than CsA in inhibiting the activation of T cells.Animal studies on MRL/lpr mice LN model demonstrated that FK506 could significantly depress the excretion of urine protein and the level of serum anti-dsDNA, inhibit glomerular cellular proliferation and formation of crescents, and reduce the deposits of immune complex.

A preliminary study showed that FK506 was significantly effective on patients with IV LN,as indicated by rapid reduction of urine protein, increase in serum albumin, decrease in auto antibodies together with remission of lesion activity of the renal tissue. However, the drawbacks of this study were the small sample size and the lack of a controlled group. Hence, a multi-center controlled study comparing FK506 with cytotoxic agents to evaluate the efficacy and safety of FK506 on patients with III or IV LN, and explore the effective range of FK506 blood concentration and the appropriate target patient population would be needed.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Female patients with a diagnosis of Systemic Lupus Erythematosus (SLE) according to the criteria of American Rheumatic Association, 1982 (Appendix 1) aged between 18-65 years, and whose score of SLE-DAI (Disease Active Index, Appendix 2) is greater than 10.
Patients diagnosed to have class III or IV LN by renal biopsy, according to the WHO classification criteria (1995, Appendix 3) within 3 month and have significant active pathological lesion.
Patients with a proteinuria ≥ 2g/24h, and an active urine sediment (Hematuria with white cells and casts in urine).
Patients who signed written informed consent form (patients less than 18 years old with their parents/legal representative's signatures), and have given their consent to follow all study procedures and follow-up.

Exclusion Criteria:

Patients who have received treatment of cytotoxic drugs such as CTX, Mycophenolate mofetil (MMF) cyclosporine for more than 1 week within three months, but Azathioprine (AZa) are accepted.
Patients with serum creatinine > 3 mg/dl（265μmol/L）.
Patients with severe infection or central nervous system symptoms.
Patients who have impaired liver function, with ALT/GPT or AST/GOT twice more than the normal upper limit or who have active hepatitis.
Patients who have abnormal glucose, with a fasted blood glucose > 6.2 mmol/L or post meal blood glucose > 11.2 mmol/L.
Patients who are pregnant or lactating.
Patients who are known to be allergic to a macrolide.
Patients who use Erythromycin, Fluconazole, Ethinylestradiol, Rifampicin, and Carbamazepine.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00302549

Locations

China, Jiangsu
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine
Nanjing, Jiangsu, China, 210002

Sponsors and Collaborators

Nanjing University School of Medicine

Sun Yat-sen University

Investigators

Study Director:

Lei-shi Li, M.D.

Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine

More Information

Responsible Party:	Nanjing University School of Medicine ( Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine )
Study ID Numbers:	NJCT-0602
Study First Received:	March 13, 2006
Last Updated:	July 14, 2008
ClinicalTrials.gov Identifier:	NCT00302549
Health Authority:	China: State Food and Drug Administration

Keywords provided by Nanjing University School of Medicine:

Tacrolimus
Cyclophosphamide
Treatment
Lupus Nephritis

Study placed in the following topic categories:

Glomerulonephritis
Autoimmune Diseases
Lupus Erythematosus, Systemic
Urologic Diseases
Lupus Nephritis

Nephritis
Connective Tissue Diseases
Tacrolimus
Cyclophosphamide
Kidney Diseases

Additional relevant MeSH terms:

Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009