| CTRI Number |
CTRI/2024/04/065206 [Registered on: 04/04/2024] Trial Registered Prospectively |
| Last Modified On: |
03/04/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
COMPARISON OF MIDODRINE+STANDARD MEDICAL THERAPY AND STANDARD MEDICAL THERAPY ALONE IN CIRRHOSIS ASSOCIATED REFRACTORY ASCITES PATIENTS |
|
Scientific Title of Study
|
AN OPEN-LABELLED BLINDED ENDPOINT RANDOMISED TRIAL (PROBE) TO ASSESS THE EFFICACY AND KINETICS OF MIDODRINE IN CIRRHOSIS ASSOCIATED REFRACTORY ASCITES PATIENTS |
| Trial Acronym |
PROBE TRIAL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr ARUN VALSAN |
| Designation |
Clinical Assistant Professor |
| Affiliation |
Amrita Institute of Medical Sciences and Research Center, Kochi |
| Address |
Department of Gastroenterology and Hepatology
Amrita Institute of Medical Sciences and Research Center, Edapally, Kochi, Kerala
Ernakulam
KERALA
682041
India |
| Phone |
8411051156 |
| Fax |
|
| Email |
drarunvalsan@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr ARUN VALSAN |
| Designation |
Clinical Assistant Professor |
| Affiliation |
Amrita Institute of Medical Sciences and Research Center, Kochi |
| Address |
Department of Gastroenterology and Hepatology
Amrita Institute of Medical Sciences and Research Center, Edapally, Kochi, Kerala
Ernakulam
KERALA
682041
India |
| Phone |
8411051156 |
| Fax |
|
| Email |
drarunvalsan@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr ARUN VALSAN |
| Designation |
Clinical Assistant Professor |
| Affiliation |
Amrita Institute of Medical Sciences and Research Center, Kochi |
| Address |
Department of Gastroenterology and Hepatology
Amrita Institute of Medical Sciences and Research Center, Edapally, Kochi, Kerala
Ernakulam
KERALA
682041
India |
| Phone |
8411051156 |
| Fax |
|
| Email |
drarunvalsan@gmail.com |
|
|
Source of Monetary or Material Support
|
| AMRITA SCHOOL OF MEDICINE, EDAPALLY, KOCHI |
|
|
Primary Sponsor
|
| Name |
Amrita School of Medicine |
| Address |
Amrita Institute of Medical Sciences and Research Center, Edappally, Kochi, Kerala |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Arun Valsan |
Amrita Hospital |
Amrita Hospital, Amrita Institute of Medical Sciences and Research Center, Edappally, Kochi, Kerala
Ernakulam
KERALA |
8411051156
drarunvalsan@gmail.com |
| MERIN P GEORGE |
Amrita Hospital |
Amrita hospital, Amrita Institute of Medical Sciences and Research Center, Edappally, Kochi, Kerala
Ernakulam
KERALA |
9562687565
merinpgeorge45@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Amrita Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: K74||Fibrosis and cirrhosis of liver, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
MIDODRINE+STANDARD MEDICAL THERAPY
|
MIDODRINE 5mg orally three times daily and dose increased by 2.5mg every fourth day after checking BP, weight and creatinine, till achieving a mean arterial pressure greater than 82 mmHg for 28 days. If MAP is above 82 mmHg, the dose doesnt increase.
SMT includes: Low-sodium diet (5g/day), salt restriction, Large-volume paracentesis, Diuretics like torsemide/lasilactone/spironolactone orally at doses 10mg/20mg/50mg once daily for 28 days |
| Comparator Agent |
STANDARD MEDICAL THERAPY |
SMT includes:
Low-sodium diet (5 g/day) salt restriction, Large-volume paracentesis, Diuretics like torsemide/lasilactone/spironolactone orally at doses 10mg/20mg/50mg once daily for 28 days |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
Definite history of cirrhosis with refractory ascites, ascites evidenced by USG and stable renal function. |
|
| ExclusionCriteria |
| Details |
Heart failure with ascites, serum creatinine greater than 1.5 mg/dl, anuria, gastrointestinal bleeding, HRS, grade 2 encephalopathy. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Control of ascites determined by change in weight, need of LVP, USG imaging. |
28 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Determine serum drug concentration of midodrine, responsiveness to midodrine by assessing mean arterial pressure, urine sodium and pottassium, renal function and liver function, assess change in serum sodium and pottasium and to assess treatment emergent ADRs. |
28 days |
|
|
Target Sample Size
|
Total Sample Size="80"
Sample Size from India="80"
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
|
Phase 4 |
|
Date of First Enrollment (India)
|
15/04/2024 |
| 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="0"
Months="7"
Days="15" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
All the patients with cirrhosis-associated refractory ascites who were admitted and came in OPD at Amrita Hospital will be screened. Those who fulfill the study inclusion criteria will be invited to participate in the study. A detailed, informed consent form will be provided. After obtaining consent from the patient (or a family member as appropriate), they will be enrolled in either the study group (Midodrine + Standard Medical Therapy) or the Standard Medical Therapy group alone (SMT) as per computer-generated randomization. In each arm, there are 40 patients, for a total of 80. All enrolled patients in the study group will be given midodrine 5mg three times daily, and the dose is increased by 2.5mg every fourth day until they achieve a mean arterial pressure of >82 mmHg, along with standard medical therapy. The standard medical therapy group for refractory ascites includes fluid management, ascites drainage, paracentesis, a low-sodium diet, and diuretics. The 8-ml blood sample will be collected from the patients in the study group on any day after the second day of administration of midodrine for therapeutic drug monitoring.
The effectiveness of midodrine will be evaluated based on the following factors: the need for large volume paracentesis, percentage change in body weight, USG, renal function, liver function, urine sodium and potassium, serum electrolytes, and adverse events that occur over the course of treatment. After 28 days, the study will be terminated. |