Assessment of Rituximab Therapeutic Response Versus Conventional Treatment

NCT ID: NCT05553496

Last Updated: 2022-09-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-25
• Study Completion Date: 2023-10-01

Brief Summary

Prospective interventional comparative study to compare the efficacy of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome including patients on triple immunosuppression protocols.

Detailed Description

A prospective randomized controlled interventional study, conducted on Refractory Nephrotic syndrome patients with failed different lines of conventional treatment.

The aim of the current study is to assess the therapeutic response of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome in terms of :

• Improvement in proteinuria.
• Relapse frequency.

Fourty patients with Refractory Nephrotic syndrome will be enrolled in the study. All participants will be previously treated with ACEi and/or ARB, for ≥3 months prior to randomization and adequate blood pressure control. Participants will be assigned randomly into two groups with 20 Refractory Nephrotic syndrome patients in each group as follow:

• Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)
• Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

The duration and severity of proteinuria are known to be surrogate markers of the progression of glomerular disease. Our approach to assess the clinical response was to evaluate estimated Glomerular filtration rate (eGFR), proteinuria and serum albumin after rituximab treatment. We classified the response into four stages :

1. No proteinuria, normal serum albumin

2. Mild proteinuria, serum albumin >30 g/l

3. Ongoing significant proteinuria, serum albumin 20-30 g/l

4. No change in proteinuria and serum albumin. Stages 1 and 2 will be interpreted as a good clinical response, whereas stages 3 and 4 will be interpreted as a poor clinical response.

A sample size of fourty patients with Refractory Nephrotic syndrome is selected to achieve confidence limit of 5%. At the end of the study, a number of data will be generated, such as:

1. Quantitative data will be summarized as means and standard deviations and/or medians and ranges.

2. Categorical data will be summarized as frequencies & percentage.

3. For measuring statistical differences between groups, categorical variables are analyzed using the chi-squared test or Fisher's exact test, whereas continuous variables are compared using Student t tests or Mann-Whitney U tests or Wilcoxon signed-rank test, as appropriate.

4. Statistical comparisons between pre- and post-treatment values are performed using the Wilcoxon signed-rank test.

5. Univariate linear regression models are used to examine the association between baseline characteristics and response to drug treatment.

6. All tests are performed at a significance level of 0.05.

Conditions

Pharmacological Action

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

RTX in Refractory Nephrotic syndrome patients on conventional treatment

Refratory Nephrotic syndrome participants will receive a 375 mg/m2 weekly rituximab for four doses, with retreatment every 2 months till 6 months regardless of proteinuria response in addition to triple optimized immunosuppression therapy including steroids ± Calcineurine inhibitors (CNI) (e.g: Tacrolimus), Mycophenloatemofetil (MMF) and Cyclophosphamide (CTX)

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)

Dexamethasone

Intervention Type: DRUG

Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

Refractory Nephrotic Syndrome patients on Conventional therapy

Nephrotic syndrome participants will receive conventional therapy treatment only including steroids ± Tacrolimus (TAC), Cyclosporine (CsA), Mycophenloatemofetil (MMF), and Cyclophosphamide (CTX) then if become refractory to conventional treatment will continue on the same treatment.

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

Interventions

Rituximab

Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)

Intervention Type: DRUG

Dexamethasone

Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

Intervention Type: DRUG

Other Intervention Names

Dexamethasone; Tacrolimus; Mycophenloatemofetil; Cyclophosphamide; Tacrolimus; Cyclosporine; Mycophenloatemofetil; Cyclophosphamide

Eligibility Criteria

Inclusion Criteria

1. Adult ≥ 18 year old and medically stable.

2. Treatment with an Angiotension converting enzyme inhibitor (ACEi) and/or Angiotension II receptor blockade (ARB), for ≥3 months prior to randomization and adequate blood pressure control or if patient is intolerant to even a very low dose of either ACEi or ARB therapy.

3. Proteinuria ≥3 g/24 h using the average from two 24-hour urine collections collected within 14 days of each other despite ARB for ≥3 months as described above.

4. Estimated GFR ≥40 ml/min/1.73 m2 while taking ACEi/ARB therapy or quantified endogenous creatinine clearance ≥40 ml/min based on a 24 h urine collection.

5. Non responsive GN patients on conventional treatment.

Exclusion Criteria

1. Autoimmune diseases.

2. Patients with presence of active infection or a secondary cause of IMN (e.g. hepatitis B, SLE, medications, malignancies).

3. Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.

4. Pregnancy or breast feeding.

5. Predisposition to drug hypersensitivity.

6. Unstable medical condition.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

shaymaa omar

Head of clinical pharmacy department at Dar Al Fouad hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

PHCL555

Identifier Type: -

Identifier Source: org_study_id