| CTRI Number |
CTRI/2022/10/046590 [Registered on: 18/10/2022] Trial Registered Prospectively |
| Last Modified On: |
22/12/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Usefulness of Tolvaptan tablet over Furosemide injection in reducing swelling in Nephrotic syndrome |
|
Scientific Title of Study
|
Efficacy and safety of oral Tolvaptan versus intravenous Furosemide in childhood Nephrotic Syndrome with edema – an Open Labelled Randomised Controlled Trial |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Aarchie Gupta |
| Designation |
Senior Resident |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9310231555 |
| Fax |
|
| Email |
gupta.aarchie@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Karalanglin Tiewsoh |
| Designation |
Associate Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research
Chandigarh
CHANDIGARH
160012
India |
| Phone |
8390880902 |
| Fax |
|
| Email |
ktiewsoh@rediffmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Aarchie Gupta |
| Designation |
Senior Resident |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research
Chandigarh
CHANDIGARH
160012
India |
| Phone |
9310231555 |
| Fax |
|
| Email |
gupta.aarchie@yahoo.com |
|
|
Source of Monetary or Material Support
|
| Post Graduate Institute of Medical Education and Research |
|
|
Primary Sponsor
|
| Name |
Department of Pediatrics |
| Address |
Room No. 4110, Level 4A, Advanced Pediatric Centre, PGIMER, Chandigarh, India 160012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Aarchie Gupta |
PGIMER, Chandigarh |
Level 5B, Advanced Pediatric centre, PGIMER, Chandigarh- 160012
Chandigarh
CHANDIGARH |
9310231555
gupta.aarchie@yahoo.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee, Post Graduate Institute of medical Education and Research, Chandigarh |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N040||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, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Furosemide |
Intravenous furosemide 3-4 mg/kg/day in two divided doses for 48 hours |
| Intervention |
Tolvaptan |
Oral tolvaptan as single daily dose based on following weight for 48 hours
- more than 15 kg body weight - 7.5 mg/day
- 15-29.9 kg body weight - 15 mg/day
- 30 kg body weight- 30 mg/day
|
|
|
Inclusion Criteria
|
| Age From |
5.00 Year(s) |
| Age To |
14.00 Year(s) |
| Gender |
Both |
| Details |
1) 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
|
|
| ExclusionCriteria |
| Details |
1) 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
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Urine output over the first 48 hours (ml/kg/hr) |
0 hours
12 hours
24 hours
36 hours
48 hours |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
• Percentage of weight loss over 48 hours
• Serum sodium every 12 hourly for 48 hours
• Urine and serum osmolality every 24 hours for 48 hours
• Urine sodium/ potassium/ creatinine every 24 hours for 48 hours
• Adverse effects
|
0 Hours
12 hours
24 hours
36 hours
48 hours |
|
|
Target Sample Size
|
Total Sample Size="70"
Sample Size from India="70"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
25/10/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
None |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
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. |