Usefulness of Tolvaptan tablet over Furosemide injection in reducing swelling in Nephrotic syndrome
- Conditions
- Nephrotic syndrome with minor glomerular abnormality, (2) ICD-10 Condition: N041||Nephrotic syndrome with focal andsegmental glomerular lesions, (3) ICD-10 Condition: N048||Nephrotic syndrome with other morphologic changes, (4) ICD-10 Condition: N049||Nephrotic syndrome with unspecified morphologic changes, (5) ICD-10 Condition: N045||Nephrotic syndrome with diffuse mesangiocapillary glomerulonephritis, (6) ICD-10 Condition: N042||Nephrotic syndrome with diffuse membranous glomerulonephritis,
- Registration Number
- CTRI/2022/10/046590
- Lead Sponsor
- Department of Pediatrics
- Brief Summary
It is an academic clinical trial to assess the efficacy and safety of oral tolvaptan versus intravenous furosemide in edematous patients with childhood nephrotic syndrome . It is an open labelled, randomised control trial. The population of the study will be children and adolescents between 5 and 14 years with childhood nephrotic syndrome. Children will be enrolled after taking the written informed consent from their parents (and assent form from children aged > 8 years. As of now, the mainstay of edema therapy in nephrotic syndrome is loop diuretics — oral and intravenous furosemide. Furosemide blocks the NKCC2 channels located in ascending limb of loop of henle and thus leads to diuresis along with natriuresis leading to the resolution of edema. However, there are various problems with its use. Firstly, furosemide, tightly bound to blood albumin, is actively secreted via organic acid pumps (OAT1 and OAT3 located in basolateral and apical surfaces respectively) in proximal tubular cells. After reaching the lumen it acts on NKCC2 channels present in the thick ascending loop of Henle. Its tubular secretion thus may be impaired in patients with severe hypoalbuminemia, resulting in diuretic resistance. Oral furosemide is the initial diuretic of choice in euvolemic patients. But, absorption of oral furosemide is hampered by gut edema commonly present in nephrotic syndrome patients presenting with edema. This necessitates a change to intravenous furosemide in most cases. Further, furosemide use is associated with kidney dysfunction or a decrease in eGFR. On the other hand, Tolvaptan is an antagonist of the AVP receptor that increases free water excretion and thus augments diuresis. Tolvaptan is an oral drug to be taken only once a day. The action of tolvaptan is independent of serum albumin levels and thus, can overcome furosemide resistance in nephrotic syndrome. In nephrotic syndrome, commonly we see hyponatremia (which is mostly dilutional). Tolvaptan by increasing free water excretion helps in normalization of serum sodium balance and provides an added benefit as compared to loop diuretics. Hence, we propose to compare the efficacy of oral tolvaptan versus intravenous furosemide in a prospective open-label randomized trial. Initially patients will receive oral furosemide and Patients not responding to oral furosemide for up to 24 hours (decrease in 3% body weight or urine output < 1 ml/kg/hour) will be randomised to one of the two arms. Group 1 will be given oral tolvaptan. Group 2 will be given intravenous furosemide. Primary outcome will be the urine output in 48 hours.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 70
- Nephrotic syndrome aged between 5 and 14 years with moderate to severe edema 2) Patients not responding to oral furosemide for up to 24 hours (decrease in 3% body weight or urine output < 1 ml/kg/hour) 3) Parents willing to give informed written consent.
- Patients with hypovolemia 2) Patients with cerebral venous sinus thrombosis 3) Serum sodium < 125 or > 140 meq/L 4) eGFR < 60 ml/min/1.73 m2 5) SGOT/SGPT > 2 ULN.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Urine output over the first 48 hours (ml/kg/hr) 0 hours | 12 hours | 24 hours | 36 hours | 48 hours
- Secondary Outcome Measures
Name Time Method •Percentage of weight loss over 48 hours •Serum sodium every 12 hourly for 48 hours
Trial Locations
- Locations (1)
PGIMER, Chandigarh
🇮🇳Chandigarh, CHANDIGARH, India
PGIMER, Chandigarh🇮🇳Chandigarh, CHANDIGARH, IndiaAarchie GuptaPrincipal investigator9310231555gupta.aarchie@yahoo.com