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CTRI Number  CTRI/2011/09/001985 [Registered on: 05/09/2011] Trial Registered Prospectively
Last Modified On: 27/08/2013
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   To study the Safety and Efficacy of GRANEXIN GEL plus Standard of Care in comparison to Standard of Care alone in the Treatment of Venous Leg Ulcer 
Scientific Title of Study   A Phase II, Randomized, Prospective, Double blind, Parallel group, Multi-center Study to determine the Safety and Efficacy of GRANEXIN GEL in the Treatment of Venous Leg Ulcers 
Trial Acronym  Nil 
Secondary IDs if Any  
Secondary ID  Identifier 
2010-VLU-001   Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Atul Gupta 
Designation  Medical Monitor 
Affiliation  Max Neeman International 
Address  Max Neeman International Ltd. MaX House, 1st Floor 1, Dr Jha Marg, Okhla - III New Delhi - 110 020

South
DELHI
110 020
India 
Phone  91-9717287654  
Fax  91-11-41001945  
Email  Atul.Gupta@neemanasia.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Dr Jayashri Krishnan 
Designation  Associate Director-Monitoring 
Affiliation  Max Neeman International 
Address  Max Neeman Medical International,No. 11 A,TNGO Colony, I Street, Nanganallur, Pin Code-600061

Chennai
TAMIL NADU
800013
India 
Phone  91-9952910703  
Fax    
Email  jkrishnan@neemanasia.com  
 
Source of Monetary or Material Support
Modification(s)  
FirstString Research, Inc., 300 West Coleman Boulevard, Suite 203, Mount Pleasant, SC 29464 
 
Primary Sponsor
Modification(s)  
Name  FirstString Research Inc 
Address  300 West Coleman Boulevard, Suite 203, Mount Pleasant, SC 29464  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Max Neeman International   Max House 1, Dr. Jha Marg, Okhla Phase III, New Delhi – 110020, India Contact No.: 91-11-40772100 Fax No.: 91-11-41814959  
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 10  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Puneet Agrawal  Chopra Super speciality Hospital  Dr.Chopra Super Specality Hospital,Deapartment of General Surgery, Gurdhuwar Road,Sadar Bazar,Agra-UP
Agra
UTTAR PRADESH 
91-9837144287
91-0562-2225879
Puneet265@yahoo.com 
Dr Mohd Yunus Salarshah  Crescent Hospital & Heart Centre  Crescent Hospital & Heart Centre,Department of General surgery, Behind mout carmel school, Near Lokmat Square,Dhantoli, Nagpur-440012, Maharastra, India
Nagpur
MAHARASHTRA 
91-9890318105
91-712-2420698
dryunus29@rediffmail.com 
Dr Hariprasad Taluru Ramachandra  K.R. Hospital  K.R. Hospital, Department of Genral Surgery, NO.979,25th Main Road Banasari 1 st Stage Opp PES college Hanumanthanagar Bangalore-560050 Karnataka, India
Bangalore
KARNATAKA 
91-9845009494
91-80-23407074
harishermi@hotmail.com 
Dr Sanjay C Desai  M. S. Ramaiah Medical College and Hospitals  M.S. Ramaiah Medical College and Hospitals, Department of Vascular and Endovascular Surgery, OPD.No. 9, New BEL road, MSRIT post,Bangalore-560054,Karnataka India
Bangalore
KARNATAKA 
91-9845290575
91-80-40528402
scdesai@hotmail.com 
DrG M Prasad  Pace Cinical Research   Consultant in Diabetiology and Cardiology Pace Cinical Research ,Center,no-53, Nanda Complex , Ramamurthy Nagar Main Road, Banaswadi, Bangalore- 560043, India
Bangalore
KARNATAKA 
91-9731911630
91-80-41626643
drgmprasad@gmail.com 
Dr Prashant Rahate  Rahate Surgical Hospital & ICU   Rahte Surgical Hospital & ICU 517, Department of General surgery, Kolba Swami square, Central Avenue, Nagpur -08
Nagpur
MAHARASHTRA 
91-9822464068
91-712-6536080
prashantrahate84@yahoo.co.in 
Dr Ajay Yadav  Sir Ganga Ram Hospital  Sir Ganga Ram Hospital,Department of Vascular and Endovascular Surgery, First Floor, Room No.1110, Old Rajendra Nagar, New Delhi 110060
Central
DELHI 
91-9717183355
91-11-25861002
ajay.vascular@gmail.com 
Dr Snehal Purandare  Smt. Kashibai Navale General Hospital  Smt Kashibai Navale General Hospital, Department of Clinical research, First Floor, 49/1, Off Westerly Bypass Highway, Narhe (Ambegaon) Pune-411041, India
Pune
MAHARASHTRA 
91-9822016991
91-20-24392311
snp2311@yahoo.co.in 
Dr R Radhakrishnan   Sri Ramachandra Medical Centre  Sri Ramachandra Medical Centre, Department of Vascular Surgery, Room No8, A2 Private Clinic, Ramasamy Udayar Block, Porur, Chennai 600116. Tamilnadu, India
Chennai
TAMIL NADU 
91-9840073083
91-44-2476-5995
rrkrishnan@hotmail.com 
Dr S R Subrammaniyan  Vijaya Hospital & Heart Foundation  Vijaya Hospital / Heart Foundation Department of Vascular surgery, Room No. C-17, Ground Floor, 180, N. S. K. Salai, Vadapalani Chennai-600026
Chennai
TAMIL NADU 
91-44-24732266
91-44-24842931
profsrs3@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
ACE Ethics Committee 232,7th Main ,80 Feet Road Subbayanapalaya Exton, Banglore-33 Karnataka,India  Approved 
Institutional Ethics Committee Rahate Surgical Hospital & ICU 517, Kolba Swami square, Central Avenue, Nagpur -08 Maharashtra, India   Approved 
Institutional Ethics Committee Chopra Super speciality Hospital 16/1 Gurudwara road, Sadar bazaar Agra, UP   Approved 
Institutional Ethics Committee Crescent Hospital & Heart Centre, Near Lokmart Square, Dhantoli, Nagpur-440012 Maharashtra, India   Approved 
Institutional Ethics Committee K.R. Hospital, NO.979,25th Main Road Banasari 1 st Stage Opp PES college Hanumanthanagar Bangalore-560050 Karnataka, India   Approved 
Institutional Ethics Committee M. S. Ramaiah Medical College and Hospitals, New BEL road, MSRIT post, Bangalore-560054 Karnataka, India   Approved 
Institutional Ethics Committee Sir Ganga Ram Hospital, Old Rajendra Nagar, New Delhi 110060 India   Approved 
Institutional Ethics Committee Smt. Kashibai Navale General Hospital, 49/1, Off Westerly Bypass Highway, Narhe (Ambegaon) Pune-411041, Maharashtra, India   Approved 
Institutional Ethics Committee Sri Ramachandra Medical Centre, Sri RamachandraUniversity, Porur, Chennai 600116. Tamilnadu, India   Approved 
Institutional Ethics Committee Vijaya Hospital & Heart Foundation Department of Vascular surgery, 180, N. S. K. Salai, Vadapalani, Chennai-600026   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Venous Leg Ulcer,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Control Group: Standard Care would be Wound debridement  Standard Care would be Wound debridement, a non-adherent dressing over the ulcer and GRANEXIN GEL, extending 0.5 inch beyond the ulcer perimeter and inflamed skin margins and a non-occlusive dressing such as fine mesh gauze folded or rolled as a bolster and a self adherent high compression multi layer elastic wrap from metatarsals to tibial plateau 
Intervention  GRANEXIN GEL   GRANEXIN GEL is a low molecular weight gap junction (ACT-1) peptide formulated in 1.25% Hydroxyethylcellulose gel for topical applications for the management of wounds. 100 μM concentration of GRANEXIN GEL will be applied at Day 0, Day 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 along with standard of care (ie) a non-adherent dressing over the ulcer and GRANEXIN GEL, extending 0.5 inch beyond the ulcer perimeter and inflamed skin margins and a non-occlusive dressing such as fine mesh gauze folded or rolled as a bolster and a self adherent high compression multi layer elastic wrap from metatarsals to tibial plateau.  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1. Male or female aged 18 years and older.

2a. Female subjects must be post-menopausal or surgically sterilized.
or
2b. Female of child-bearing potential must have negative pregnancy test at screening, and agrees to use hormonal contraceptive or intra-uterine device (IUD) or diaphragm with spermicide or condom with spermicide or abstinence throughout the study.

3. Subjects with ulcers of venous origin, as clinically determined by the investigator by a positive venous reflux test (venous refilling <20 seconds) using Doppler ultrasound for at least 4 weeks prior to screening day, which have not adequately responded to conventional ulcer therapy.

4. Ulcers that extend through the epidermis but not through muscle, tendon, or bone (Stage II or III ulcers as defined by the IAET).

5. Surface ulcer between 0.5 cm2 and 40 cm2 post debridement.

6. Signed informed consent form.
 
 
ExclusionCriteria 
Details  1. Decrease or increase in the ulcer size by 30% or more during 7 day screening period.
2. Cannot tolerate or comply with compression therapy.
3. An ulcer which shows signs of severe clinical infection, defined as pus oozing from ulcer site.
4. The ulcer to be treated requires operative debridement.
5. An ulcer positive for _-hemolytic streptococcus upon culture.
6. The ulcer has more than 50% slough, significant necrotic tissue, osteomyelitis, bone, tendon, or capsule exposure or avascular ulcer beds.
7. Highly exuding wounds (wounds that require a daily dressing change).
8. ABPI 0.65.
9. Subjects with active systemic infections.10. Subjects with clinically significant medical conditions as determined by the Investigator which would impair wound healing including renal, hepatic, hematologic, neurologic or immune disease. Examples include but are not limited to:
a. Renal insufficiency as an estimated GFR which is 30 mL/min/1.7m2.b. Abnormal blood biochemistry defined as 3 times that of the upper limit of the normal range.c. Hepatic insufficiency defined as total bilirubin 2 mg/dL or serum albumin 25 g/L.d. HbA1c 9.0%.e. Hemoglobin 10 g/dL.f. Hematocrit 0.30. g. Platelet count 100,000.
11. Presence of an active systemic or local cancer or tumor of any kind (with the exception of non-melanoma skin cancer).
12. Subjects with active osteomyelitis of the study foot.
13. Subjects with severe rheumatoid arthritis (with more than 20 persistently inflamed joints, or below lower normal limit blood albumin level, or evidence of bone and cartilage damage on x-ray, or inflammation in tissues other than joints) and other collagen vascular diseases.
14. Subjects with active connective tissue disease.
15. Treatment with systemic corticosteroids (15 mg/day), or current immunosuppressive agents.
16. Previous or current radiation therapy or likelihood to receive this therapy during study participation.
17. Pregnant or nursing subjects.
18. Known prior inability or unavailability to complete required study visits during study participation.
19. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse problem, determined from the subjects medical history, which, in the opinion of the Investigator, may pose a threat to subject compliance.
20. Use of any investigational drug or therapy within the 28 days prior to screening.
21. Any other factor which may, in the opinion of the Investigator, compromise participation and follow-up in this study. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
The mean percent wound closure.   week 12 from baseline.  
 
Secondary Outcome  
Outcome  TimePoints 
Mean percent wound closure  4 weeks from baseline 
Time taken for 50% wound closure.   from day 3 till study exit 
Subject self-assessment of intensity of pain.   from day 3 till study exit 
Time to complete wound closure where complete wound closure will be defined as 100% epithelialization of the wound and the absence of drainage from the wound.  from day 3 till study exit 
 
Target Sample Size   Total Sample Size="92"
Sample Size from India="92" 
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)
Modification(s)  
11/10/2011 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   none as yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   This Phase II, prospective, study is designed as a multicenter, double blind, parallel group study in which subjects with venous leg ulcers will be randomly allocated to receive 100μM concentration GRANEXIN GEL plus Standard of Care (SoC) as compared to Standard of Care alone. The total study duration for efficacy assessments is 12 weeks with additional 12 weeks follow up for safety evaluations. The patients would be treated with 100 μM concentration of GRANEXIN GEL will be applied at Day 0, Day 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 along with standard of care and the control group would be treated with standard care alone. The endpoint of the study would be, mean percent of wound closure from baseline, Subject self-assessment of intensity of pain, and complete wound closure, defined as 100% epithelialization of the wound and the absence of drainage from the wound 
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