Pharmacological ActionPhase 2/3NCT05553496
Assessment of Rituximab Therapeutic Response Versus Conventional Treatment
A Phase 2/3 study testing Rituximab and Dexamethasone in people with Pharmacological Action, run by Ain Shams University.
Trial summary
Prospective interventional comparative study to compare the efficacy of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome including patients on triple immunosuppression protocols. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pharmacological Action
- What is being tested?
- Rituximab and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- 25 Sep 2022to 1 Oct 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult ≥ 18 year old and medically stable.
- 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.
- 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.
- 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.
- Non responsive GN patients on conventional treatment.
Who cannot join
- Autoimmune diseases.
- Patients with presence of active infection or a secondary cause of IMN (e.g. hepatitis B, SLE, medications, malignancies).
- Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
- Pregnancy or breast feeding.
- Predisposition to drug hypersensitivity.
- Unstable medical condition.
About this study
Official title: Assessment of Rituximab Therapeutic Response Versus Conventional Treatment in the Management of Refractory Nephrotic Syndrome
Prospective interventional comparative study to compare the efficacy of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome including patients on triple immunosuppression protocols.
Read the 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 :
- No proteinuria, normal serum albumin
- Mild proteinuria, serum albumin >30 g/l
- Ongoing significant proteinuria, serum albumin 20-30 g/l
- 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:
- Quantitative data will be summarized as means and standard deviations and/or medians and ranges.
- Categorical data will be summarized as frequencies \& percentage.
- 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.
- Statistical comparisons between pre- and post-treatment values are performed using the Wilcoxon signed-rank test.
- Univariate linear regression models are used to examine the association between baseline characteristics and response to drug treatment.
- All tests are performed at a significance level of 0.05.
- Conditions
- Pharmacological Action
- Being tested
- Rituximab, Dexamethasone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Dexamethasone, Tacrolimus, Mycophenloatemofetil, Cyclophosphamide
Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)
DexamethasoneDrug
Also called Tacrolimus, Cyclosporine, Mycophenloatemofetil, Cyclophosphamide
Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)
| Study group | Role | What they receive |
|---|---|---|
| RTX in Refractory Nephrotic syndrome patients on conventional treatment | Active comparator | 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) Receives: Drug: Rituximab; Drug: Dexamethasone |
| Refractory Nephrotic Syndrome patients on Conventional therapy | Active comparator | 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. Receives: Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
The primary end point is Complete or Partial remission at 6 months after randomization. Complete remission (CR) is defined as UP ≤0.3 g/24 h and serum albumin ≥3.5 g/dl while Partial remission (PR) is defined as Reduction in baseline UP of ≥50% plus final UP ≤3.5 g/24 h but >0.3 g/24 h. The patient who will be Non-responsive to therapy is defined as Reduction in baseline UP of <25% (includes increase in UP) after 6 months of immunosuppression and the patient who will enter in the relapsed phase is defined as development of nephrotic range proteinuria following CR or PR, i.e. >3.5 g/24 h.
Measured: 6 months
Secondary outcomes (6)
A) Late Remissions:
The first 6 months of the study will be considered the treatment period, while the remaining 6 months will be considered an observational period.So we will monitor the patients for CR or PR at 6, 9, and 12 months after randomization.
Measured: 6, 9, and 12 months after randomization.
B) Relapse state:
Relapse state of the patient will be assessed at month 12 after randomization (Urine Protein (UP) >3.5 g/24 h after earlier CR or PR).
Measured: 12 months after randomization
C) Response Treatment Time:
The response time will be assessed by measuring the duration of clinical response to RTX in patients who had on going CR or PR.
Measured: 12 months after randomization
D) End Stage Renal Disease (ESRD):
The patients who developed ESRD will be reviewed in this study.
Measured: 12 months after randomization
E) Renal Function:
The effect of treatment on renal function will be assessed every 3 months by calculating the estimated GFR (eGFR) with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula from baseline to 6 months.
Measured: 6 months after randomization
F) Adverse events:
Patients will be educated about adverse effects of the drugs and will be required to report the occurrence of any of them.
Measured: 6, 9, and 12 months after randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start25 Sep 2022 (estimated)
- Primary completion1 Apr 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pharmacological ActionStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, shaymaa omar, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05553496
- Sponsor's protocol ID
- PHCL555
- Status last verified
- Sep 2022
- First submitted
- 15 Sep 2022
- Last updated
- 23 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Rituximab Therapeutic Response Versus Conventional Treatment in the Management of Refractory Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT05553496
- Acronym / sponsor ID
- PHCL555
- Conditions
- Pharmacological Action
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 25 Sep 2022 (estimated)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 23 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 :
- No proteinuria, normal serum albumin
- Mild proteinuria, serum albumin >30 g/l
- Ongoing significant proteinuria, serum albumin 20-30 g/l
- 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:
- Quantitative data will be summarized as means and standard deviations and/or medians and ranges.
- Categorical data will be summarized as frequencies \& percentage.
- 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.
- Statistical comparisons between pre- and post-treatment values are performed using the Wilcoxon signed-rank test.
- Univariate linear regression models are used to examine the association between baseline characteristics and response to drug treatment.
- All tests are performed at a significance level of 0.05.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RTX in Refractory Nephrotic syndrome patients on conventional treatment | Active comparator | Drug: Rituximab, Drug: DexamethasoneRefratory 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) |
| Refractory Nephrotic Syndrome patients on Conventional therapy | Active comparator | Drug: DexamethasoneNephrotic 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult ≥ 18 year old and medically stable.
- 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.
- 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.
- 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.
- Non responsive GN patients on conventional treatment.
Key exclusion criteria (6 listed)
- Autoimmune diseases.
- Patients with presence of active infection or a secondary cause of IMN (e.g. hepatitis B, SLE, medications, malignancies).
- Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.
- Pregnancy or breast feeding.
- Predisposition to drug hypersensitivity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Dexamethasone, Tacrolimus, Mycophenloatemofetil, CyclophosphamideGroup (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients) | Drug | RTX in Refractory Nephrotic syndrome patients on conventional treatment |
| DexamethasoneAlso: Tacrolimus, Cyclosporine, Mycophenloatemofetil, CyclophosphamideGroup (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients) | Drug | RTX in Refractory Nephrotic syndrome patients on conventional treatment, Refractory Nephrotic Syndrome patients on Conventional therapy |
Primary outcome
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.
Time frame: 6 months
The primary end point is Complete or Partial remission at 6 months after randomization. Complete remission (CR) is defined as UP ≤0.3 g/24 h and serum albumin ≥3.5 g/dl while Partial remission (PR) is defined as Reduction in baseline UP of ≥50% plus final UP ≤3.5 g/24 h but >0.3 g/24 h. The patient who will be Non-responsive to therapy is defined as Reduction in baseline UP of <25% (includes increase in UP) after 6 months of immunosuppression and the patient who will enter in the relapsed phase is defined as development of nephrotic range proteinuria following CR or PR, i.e. >3.5 g/24 h.
6 secondary outcomes
A) Late Remissions:
Time frame: 6, 9, and 12 months after randomization.
B) Relapse state:
Time frame: 12 months after randomization
C) Response Treatment Time:
Time frame: 12 months after randomization
D) End Stage Renal Disease (ESRD):
Time frame: 12 months after randomization
E) Renal Function:
Time frame: 6 months after randomization
F) Adverse events:
Time frame: 6, 9, and 12 months after randomization.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituximab and Dexamethasone in people with Pharmacological Action, run by Ain Shams University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2022.