CTRI Number |
CTRI/2021/07/034907 [Registered on: 15/07/2021] Trial Registered Prospectively |
Last Modified On: |
15/07/2021 |
Post Graduate Thesis |
Yes |
Type of Trial |
Interventional |
Type of Study
|
Drug |
Study Design |
Randomized, Parallel Group Trial |
Public Title of Study
|
Role of combination antifungal therapy (Liposomal Amphotericin B and Posaconazole) in Mucormycosis |
Scientific Title of Study
|
A prospective, open-label, randomisation-controlled trial of combination antifungal therapy (Liposomal Amphotericin B and Posaconazole) vs single antifungal (Liposomal Amphotericin B) for initial treatment in Mucormycosis (ComPLiMenT Trial) |
Trial Acronym |
ComPLiMenT Trial |
Secondary IDs if Any
|
Secondary ID |
Identifier |
NIL |
NIL |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
Name |
Dr Ved Prakash Meena |
Designation |
Assistant professor |
Affiliation |
All India Institute of Medical Sciences, New Delhi |
Address |
Medicine office, Department of Medicine, 3rd floor, Teaching block, AIIMS, New Delhi (110029)
South DELHI 110029 India |
Phone |
9911870646 |
Fax |
|
Email |
vpmahar05@gmail.com |
|
Details of Contact Person Scientific Query
|
Name |
Dr Ved Prakash Meena |
Designation |
Assistant professor |
Affiliation |
All India Institute of Medical Sciences, New Delhi |
Address |
Medicine office, Department of Medicine, 3rd floor, Teaching block, AIIMS, New Delhi (110029)
DELHI 110029 India |
Phone |
9911870646 |
Fax |
|
Email |
vpmahar05@gmail.com |
|
Details of Contact Person Public Query
|
Name |
Dr Rohit Kumar |
Designation |
Senior resident ( infectious diseases) |
Affiliation |
All India Institute of Medical Sciences, New Delhi |
Address |
Medicine office, Department of Medicine, 3rd floor, Teaching block, AIIMS, New Delhi (110029)
South DELHI 110029 India |
Phone |
9999597994 |
Fax |
|
Email |
drrohitkgarg@gmail.com |
|
Source of Monetary or Material Support
|
|
Primary Sponsor
|
Name |
AIIMS Department of Medicine |
Address |
Medicine office, Department of Medicine, AIIMS, New Delhi |
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 |
Dr Ved Prakash Meena |
AIIMS, New Delhi |
Medicine Office, Department of Medicine, 3rd floor, Teaching block South DELHI |
9911870646
vpmahar05@gmail.com |
|
Details of Ethics Committee
|
No of Ethics Committees= 1 |
Name of Committee |
Approval Status |
AIIMS Institutional Ethics committee |
Approved |
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
|
Health Type |
Condition |
Patients |
(1) ICD-10 Condition: B46||Zygomycosis, |
|
Intervention / Comparator Agent
|
Type |
Name |
Details |
Intervention |
Combination of Liposomal Amphotericin B plus Tablet Posaconazole |
In intervention arm, study particiants will receive combination of Liposomal Amphotericin B plus Tablet Posaconazole
Dose - 3mg/Kg iv OD for 3 weeks in initial therapy
Tab Posaconazole 300 mg BD on Day 1 followed by 300 mg OD x 3 weeks |
Comparator Agent |
Monotherapy Liposomal Amphotericin B |
In control arm, study particiants will recieve only Liposomal Amphotericin B in initial therapy
Dose - 3mg/Kg iv OD for 3 weeks in initial therapy |
|
Inclusion Criteria
|
Age From |
18.00 Year(s) |
Age To |
75.00 Year(s) |
Gender |
Both |
Details |
All patients aged 18 years or more, newly diagnosed probable (clinical and radiological) or proven invasive mucormycosis will be included. |
|
ExclusionCriteria |
Details |
1 Patients not willing to consent.
2 Patients with more than 5 days of primary antifungal therapy
3 Patients unable to receive enteral medications.
4 Co-existing conditions precluding the use of both Amphotericin B or Posaconazole
a Liposomal Amphotericin B – history of hypersensitivity
b Posaconazole – H/o hypersensitivity (other azoles), Concurrent drugs (Sirolimus: can result in sirolimus toxicity; CYP3A4 substrates (pimozide, quinidine): can result in QTc interval prolongation and cases of Torsades de Pointes; HMG-CoA Reductase Inhibitors Primarily Metabolized Through CYP3A4: can lead to rhabdomyolysis, Ergot alkaloids: can result in ergotism drug interactions); Transaminitis ( AST or ALT >5 times ULN)
5 Patients who are critically ill/ hemodynamic instability
6 Patients with active moderate and severe COVID19 illness at the time of recruitment
7 Breastfeeding/ pregnancy
8 Patient enrolled in other ongoing prospective drug trials for IM
|
|
Method of Generating Random Sequence
|
Permuted block randomization, variable |
Method of Concealment
|
On-site computer system |
Blinding/Masking
|
Open Label |
Primary Outcome
|
Outcome |
TimePoints |
Complete or partial response at week 3 |
3 weeks |
|
Secondary Outcome
|
Outcome |
TimePoints |
1.Complete response at week 6 and week 12
|
6 weeks, 12 weeks |
2.Increased survival at week 12, 6 months and 12 months.
|
3, 6 and 12 months |
3.Reduction in all-cause mortality |
12 months |
|
Target Sample Size
|
Total Sample Size="40" Sample Size from India="40"
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 2/ Phase 3 |
Date of First Enrollment (India)
|
19/07/2021 |
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)
|
Not Applicable |
Recruitment Status of Trial (India) |
Not Yet Recruiting |
Publication Details
|
Nil |
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
|
Mucormycosis is caused by fungi of the order Mucorales. It is characterized by an
angio-invasive disease leading to necrotizing arteritis of involved tissues. It
most commonly affects immunocompromised patients. Untreated
mucormycosis is almost always fatal.
Even after more than one year
following the origin of the pandemic, the pathogenesis of COVID19 remains
partially understood and understanding of the same continues to evolve with
time. As the highly infectious virus continues to give rise to new cases globally,
one of the emerging concerns is
serious upsurge in the number of cases of mucormycosis. It remains to be seen if this
increasing incidence of mucormycosis in COVID19 is related to the illness
itself, the steroids and immunomodulators administered for treatment, or the
worsening of underlying predisposing factors in the socio-economic upheaval
caused by the pandemic.
The management of mucormycosis includes a
combination of surgical resection of affected tissues combined with antifungal
therapy. Polyenes (Amphotericin B) form the backbone of antifungal therapy in
mucormycosis and have been the standard of care for so many years. In addition, newer agents
such as Posaconazole (or isavuconazole) have been approved as salvage therapy. Unfortunately, despite adequate surgery and initial management with Amphotericin B, mortality
rates in cases of mucormycosis are remarkably high. Considering the poor
outcome, there is increasing interest in focusing on the role of combination
antifungal therapy in the treatment of mucormycosis. The ongoing COVID19 pandemic
provides us a grim scenario in terms of the number of cases of mucormycosis.
However, the current situation also provides us with an opportunity to conduct a
prospective clinical trial to evaluate the role of combination therapy of
polyenes and azoles.
We intend to conduct
following prospective, open-label,
randomized control trial to evaluate the benefit of combination antifungal
therapy in the treatment of mucormycosis. |