CTRI/2020/02/023409 [Registered on: 18/02/2020] Trial Registered Prospectively
Last Modified On:
16/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
The DIVERSE Trial:
Study to Evaluate the Efficacy and Safety of Dalbavancin in Comparison with Comparator Regimen (Vancomycin Followed by Linezolid) for the Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs).
Scientific Title of Study
A Phase III Randomized, Multicenter, Open Label, Parallel Groups, Non-inferiority Study to Evaluate the Efficacy and Safety of Dalbavancin in Comparison with Comparator Regimen (Vancomycin Followed by Linezolid) for the Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Chandu Devanpally
Designation
Managing Director
Affiliation
Ardent Clinical Research Services
Address
Ardent Clinical research Services,
Office No. 318, level 3, Next to frankfinn, Connaught Place, Bund Garden Road, Pune-01, MH, India. Pune MAHARASHTRA 411001 India
Phone
02048603277
Fax
-
Email
cdevanpally@ardent-cro.com
Details of Contact Person Scientific Query
Name
Dr Adarsh Shetty
Designation
Senior Manager – Medical Affairs
Affiliation
Gufic Biosciences Limited
Address
Gufic Biosciences Limited
Subhash Road-A Block Vile Parle East Mumbai,
Maharashtra,
India – 400057 Mumbai MAHARASHTRA 400057 India
Phone
02267261000
Fax
-
Email
medicalaffairs@guficbio.com
Details of Contact Person Public Query
Name
Pranjal Ausekar
Designation
Project Manager
Affiliation
Ardent Clinical Research Services
Address
Ardent Clinical research Services,
Office No. 318, level 3, Next to frankfinn, Connaught Place, Bund Garden Road, Pune-01, MH, India. Pune MAHARASHTRA 411001 India
Phone
02048603477
Fax
-
Email
pranjal@ardent-cro.com
Source of Monetary or Material Support
Gufic Biosciences Ltd.Subhash Road-A Block Vile Parle East Mumbai, Maharashtra,
India – 400057
Primary Sponsor
Name
Gufic Biosciences Ltd
Address
Subhash Road-A Block Vile Parle East Mumbai, Maharashtra,
India – 400057
Acharya Vinoba Bhave Rural Hospital, Jawah Datta Meghe Institute of Medical Science
Room No.: 05
Department: Old semi Paying
Division: Clinical research Department, Sawangi-Wardha-442004 Wardha MAHARASHTRA
7353340479 - jay.45appu@gmail.com
Dr Pankaj Kumar
All India Institute of Medical Sciences
Room No. 451, 4th floor, academic divisionAll India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar-751019 Khordha ORISSA
9438884253 - drpkushwaha@gmail.com
Dr Lata Bhoir
BJMC Medical College & Sassoon General Hospital
Department of Surgery,
Department No. 10,
1st Floor main building,
BJ medical college and
Sassoon general hospital, Jaiprakash Narayan Road, Near Pune Railway Station
Pune-411001,MH,India Pune MAHARASHTRA
9552189336 - lbhoir03@gmail.com
Dr Sunil Kumar Singh
Dr. Ram Manohar Lohia Institute of Medical Sciences
Department of General Surgery, Vibhuti Khand, Gomti nagar, Lucknow 226010 Lucknow UTTAR PRADESH
918957386405 - sunilkamal.singh@gmail.com
Dr Prathvi Shetty
Father Muller Research centre
Father Muller Road, Kankanady, Mangalore -57 5002, Karnataka, India Dakshina Kannada KARNATAKA
9886839423
prathviz@fathermuller.in
Dr Suraj Kumar Pattnayak
Govt Medical college & Govt General Hospital, Srikakulam
Department of Surgery, Srikakulam. Srikakulam ANDHRA PRADESH
8942279033 - gghsrikakulam@gmail.com
Dr Madhu CP
JSS Hospital
CDSA-CCRE Office
2nd floor, Master health Checkup Area,MG Road, Near Agrahara Circle, Ramachandra Agrahara, Mysore, Karnataka 570004 Mysore KARNATAKA
9448383898 - drcpmadhu@gmail.com
Dr Mruttyunjay Uppin
Kle Societys hospital and Medical research centre
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre, Site Management office, 2nd Floor, Saraswati Ward, Near Psychiatric ward, Nehrunagar, Belgavi-590010, Karnataka-India. Belgaum KARNATAKA
7353340479
jay.45appu@gmail.com
Dr Minakshi Gadhire
Lokmanya Tilak Municipal Medical College & Lokmanya Tilak General Hospital
Lokmanya Tilak Municipal Medical College & Lokmanya Tilak General Hospital Dr.Ambedkar Marg, Sion, Mumbai 400022, Maharashtra, India Mumbai MAHARASHTRA
9820556928 - gadhireminakshi@yahoo.in
Dr Shivakumara
Madhu Super Specialty Hospital and Research Institute
No. 58, M, Muniyappa complex, Magadi Main Road, Agrahara, Dasarahalli, Vijayanagar, Bengaluru – 560079, Karnataka. Bangalore KARNATAKA
9060102094 - drshivakumargowda80@gmail.com
Dr Chetan Patel
Nirmal Hospital Pvt. Ltd
Room No. 109 OPD, Department of Surgery, Nirmal Hospital Pvt. Ltd, Ring Road, Surat- 395002,Gujarat Surat GUJARAT
2612333999 2614089999 drcrpatel71@gmail.com
Dr Arunanshu Behra
Post Graduate Institute of Medical Education And Research
Department of General Surgery
5th floor, F block, Nehru hospital, Sector 12, Post Graduation Institute of Medical Education And Research, Sector 12, Chandigarh,Punjab- 160012 Panchkula HARYANA
2756638 - abe190859@yahoo.com
Dr Prashant V Rahate
Rahate Surgical Hospital
Rahate Surgical Hospital, Near telephone exchange square, Old Mangalwari, Central Avenue, Nagpur Maharashtra 440008 Nagpur MAHARASHTRA
The Institutional Ethics committee, GMC, Srikakulam
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: L089||Local infection of the skin and subcutaneous tissue, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Dalbavancin
Dalbavancin is a novel antibiotic.Each vial of Dalbavancin contains 500 mg powder, which is to be reconstituted and further diluted for IV infusion by using water for injection IP q.s. On day one 1000 mg dose will be given to the patients. On day 8 single injection of 500 mg will be given in the morning.
Comparator Agent
Vancomycin 1000 mg & Lineolid 600 mg
Patients will receive 1000mg or 15mg/kg Vancomycin twice daily for at least 3 days. Later as per PI discretion 600 mg Linezolid will be given after every 12 hrs. till day 14.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Subjects must sign Informed Consent (ICF) prior to any evaluation and participation in the trial.
2. Male or female patients with age 18 - 65 years of age.
3. Patients who require hospitalization or already hospitalized patients with diagnosis of ABSSSIs.
4. Patients having an ABSSSIs confirmed to be caused by gram-positive bacteria defined for purposes of this study as an infection either involving deeper soft tissue or requiring significant surgical intervention. Patients with below mention condition will be included:
a. Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which:
i. Requires surgical incision and drainage, and
ii. Is associated with cellulitis such that the total affected area involves at least 75 cm2 of erythema, andiii. Alternatively, involves the central face and is associated with an area of erythema of at least 50 cm2.
b. Surgical site or traumatic wound infection characterized by purulent drainage with surrounding erythema, edema and/or induration which occurred within 30 days after the trauma or surgery and is associated with cellulitis such that
i. The total affected area involves at least 75 cm2 of erythema, and
ii. Alternatively, involves the central face and is associated with an affected area of at least 50 cm2.
c. Cellulitis, defined as a diffuse skin infection characterized by spreading areas of erythema, edema and/or induration and
i. Is associated with erythema that involves at least 75 cm2 of surface area, or
ii. Alternatively, cellulitis of the central face that is associated with an affected area of at least 50 cm2. (Note: Patients with Diabetes Mellitus having any of above-mentioned conditions OR patients with diabetic foot ulcer can also be included in the study).
5. Patients must be present with at least two local signs and symptoms of ABSSSIs in addition to erythema.
a) Purulent drainage/discharge
b) Fluctuance
c) Heat/localized warmth
d) Tenderness to palpation
e) Swelling/induration
6. Patients must present with at least one of the following systemic signs of infection:
i. An elevated body temperature ≥ 38°C/100.4°F as measured by the patient/caregiver or investigator within 24 hours of baseline.
ii. White blood cell count > 12,000 cells/mm3.
7. Requires a minimum of 3 days of IV therapy.
8. Patient willing and able to comply with study procedures.
ExclusionCriteria
Details
1. Infections caused exclusively by gram-negative bacteria or presence of gram-negative bacteria even in the presence of gram-positive bacteria and infections caused by fungi, whether alone or in combination with a bacterial pathogen.
2. Gram-negative bacteremia, even in the presence of gram-positive infection or gram-positive bacteremia.
Note: If a gram-negative bacteremia develops during the study or is subsequently found to have been present at Baseline, the patient should be removed from study treatment and receive appropriate antibiotics to treat the gram-negative bacteremia. Such patients must have an EOT visit performed within 72 hours after discontinuing study medication but are required to have AEs reported through safety follow-up visit and a patient status at safety follow-up visit.
3. Subject with a contra-indication to dalbavancin, vancomycin, linezolid or any required study drug.
4. Patients with sustained shock, defined as systolic blood pressure < 90 mm Hg for more than 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion, or need for sympathomimetic agents to maintain blood pressure.
5. Participation in another study of an investigational drug or device within 30 days. 6. Patient with estimated creatinine clearance < 50 ml/min.
7. Receipt of a systemically or topically administered antibiotic with a gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the ABSSSIs within 14 days prior to randomization, except receipt of a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug 3 or more days prior to randomization.
8. Patients with evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis, endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis.
9. Venous catheter entry site infection.
10. Infections involving perirectal abscess or a decubitus ulcer.
11. Patient with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.
12. Patients whose ABSSSIs is the result of having sustained full or partial thickness burns.
13. Patients with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of < 45 mm Hg, ankle brachial index < 0.5, and/or critical ischemia as assessed by a vascular surgeon.
14. Patients with superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure.
15. Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.
16. Anticipated need of antibiotic therapy for longer than 14 days.
17. Patients who are placed in a hyperbaric chamber as adjunctive therapy for ABSSSIs.
18. More than 2 surgical interventions for ABSSSIs anticipated.
19. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity).
20. Absolute neutrophil count < 500 cells/mm3. 21. Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.
22. Patients with a recent bone marrow transplant (in post-transplant hospital stay). 23. Patients receiving oral steroids > 20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation.
24. Life expectancy less than 3 months with rapid fatal illness.
25. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
26. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
1. To evaluate the early clinical efficacy of Dalbavancin (after 72 hours of therapy) in comparison with comparator regimen for the treatment of patients with a suspected or proven gram-positive ABSSSIs.
1. To evaluate the clinical efficacy of Dalbavancin at the end of treatment visit (EOT) compared to the comparator regimen.
2. To evaluate the clinical efficacy of dalbavancin at the follow up visits compared to the comparator regimen.
3. To evaluate the safety and tolerability of dalbavancin to that of comparator regimen.
4. To compare the per-patient microbiological efficacy of dalbavancin to the comparator regimen.
Secondary Outcome
Outcome
TimePoints
1) Clinical status at the EOT visit (study Day 14). 2) Clinical status at follow up visit.
Clinical Status at 72 hours after the start of therapy and at the end of treatment i.e. Day 8 for IP group and day 14 for Comparator group.
Target Sample Size
Total Sample Size="268" Sample Size from India="268" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="268"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
An Open lable randomized active controlled phase III clinical trial is designed to evaluate safety & efficacy of Dalbavancin when compared with Vancomycin & Linezolid in patients with ABSSSI. 1000 mg Dalbavancin will be given to 134 subjects intravenously on day 1 and 500 mg Dalbavancin on day 8. 134 patients in control group will initially receive 1000 mg Vancomycin intravenously twice daily for 3-4 days. Later based on investigators discretion 600 mg Linezolid will be administered after every 12 hours till day 14. Subjects who meets all the inclusion criteria and who does not meet any of the study exclusion criteria will be enroled in he study. Haematology, biochemistry, blood culture, Hs-C reactive protein, infection site assessment, fasting glucose, ECG, Urine analysis will be performed to evaluate clinical status of the ABSSSI patients.