Clinical trial NCT05553496: Assessment of Rituximab Therapeutic Response Versus Conventional Treatment
Official title: Assessment of Rituximab Therapeutic Response Versus Conventional Treatment in the Management of Refractory Nephrotic Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Pharmacological Action
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-09-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The effectiveness of either conventional therapy alone or Rituximab as an add on therapy will be assessed by measure of Remission sate of the patient.
timeFrame: 6 months
Secondary outcomes:
measure: A) Late Remissions:
timeFrame: 6, 9, and 12 months after randomization.
measure: B) Relapse state:
timeFrame: 12 months after randomization
measure: C) Response Treatment Time:
timeFrame: 12 months after randomization
measure: D) End Stage Renal Disease (ESRD):
timeFrame: 12 months after randomization
measure: E) Renal Function:
timeFrame: 6 months after randomization
measure: F) Adverse events:
timeFrame: 6, 9, and 12 months after randomization.
Other outcomes:
Locations:
Study officials:
References: