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CTRI Number  CTRI/2024/03/064313 [Registered on: 18/03/2024] Trial Registered Prospectively
Last Modified On: 17/03/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Other (Specify) [Q-switched Nd:YAG laser 1064 nm]  
Study Design  Other 
Public Title of Study   Effectiveness of LASER in pigmented purpuric dermatosis – a placebo-controlled split-limb trial 
Scientific Title of Study   Effectiveness of Q-Switched Nd:YAG LASER in the treatment of pigmented purpuric dermatosis – a placebo-controlled split-limb trial 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  DR. ANIRBAN MUKHERJEE 
Designation  Senior resident 
Affiliation  Department of Dermatology, Bankura Sammilani Medical College 
Address  Room number 92, Department of Dermatology, Bankura Sammilani Medical College, Bankura Sammilani Medical College road, Kenduadihi, Bankura

Bankura
WEST BENGAL
722102
India 
Phone  9123799162  
Fax    
Email  mukherjeeanirban91@gmail.com  
 
Details of Contact Person
Scientific Query  
Name  DR. ANIRBAN MUKHERJEE 
Designation  Senior resident 
Affiliation  Department of Dermatology, Bankura Sammilani Medical College 
Address  Room number 92, Department of Dermatology, Bankura Sammilani Medical College road, Kenduadihi, Bankura

Bankura
WEST BENGAL
722102
India 
Phone  9123799162  
Fax    
Email  mukherjeeanirban91@gmail.com  
 
Details of Contact Person
Public Query  
Name  DR. ANIRBAN MUKHERJEE 
Designation  Senior resident 
Affiliation  Department of Dermatology, Bankura Sammilani Medical College 
Address  Room number 92, Department of Dermatology, Bankura Sammilani Medical College road, Kenduadihi, Bankura

Bankura
WEST BENGAL
722102
India 
Phone  9123799162  
Fax    
Email  mukherjeeanirban91@gmail.com  
 
Source of Monetary or Material Support  
Bankura Sammilani Medical College 
 
Primary Sponsor  
Name  Bankura Sammilani Medical College 
Address  Bankura Sammilani Medical College road, Kenduadihi, Bankura, PIN - 722102 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Anirban Mukherjee  Bankura Sammilani Medical College  Room number 92, Department of Dermatology, Bankura Sammilani Medical College, Bankura Sammilani Medical College road, Kenduadihi, Bankura, PIN - 722102
Bankura
WEST BENGAL 		 9123799162

mukherjeeanirban91@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
INSTITUTIONAL ETHICS COMMITTEE, BANKURA SAMMILANI MEDICAL COLLEGE  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: L817||Pigmented purpuric dermatosis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Placebo  Blank fire by laser machine will be given as placebo once monthly for 4 months. 
Intervention  Q switched neodymium doped yttrium aluminum garnet laser  Q switched neodymium doped yttrium aluminum garnet laser at 1064 nanometer with fluence 600 milijoule per pulse and spot size 5 milimetre once monthly for 4 months 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  Age more than 18 years to 80 years.
Pigmented purpuric dermatosis patients who have not received any treatment since 1 month.
Pigmentation present bilaterally on the lower limbs.
 
 
ExclusionCriteria 
Details  Pregnant and lactating women.
Patients having pigmented purpuric dermatosis at sites other than lower limbs.
Those having any skin disease other than pigmented purpuric dermatosis on the lower limb(s).
Patients with psychiatric disorders.
Participation in any clinical trial within the last 3 months.
Non-consenting patients
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant Blinded 
Primary Outcome  
Outcome  TimePoints 
The Q switched neodymium doped yttrium aluminum garnett laser will be more effcetive in reducing pigmentation of pigmented purpuric dermatosis , compared to placebo on the basis of decline in skin hyperpigmentation index.  16 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
The safety of Q switched neodymium doped yttrium aluminum garnett laser will be evaluated in patients with pigmented purpuric dermatosis , compared to placebo on the basis of adverse events noted.  16 weeks 
 
Target Sample Size   Total Sample Size="20"
Sample Size from India="20" 
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 1/ Phase 2 
Date of First Enrollment (India)   25/03/2024 
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="1"
Months="0"
Days="0" 
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  

BACKGROUND OF RESEARCH:

A) RATIONALE OF STUDY:

Pigmented purpuric dermatosis (PPD) is a group of diseases manifested as multiple petechial spots because of capillaritis[1]. Hyperpigmentation resulting from PPD can be of cosmetic concern for patients and its treatment is challenging. A variety of topical and systemic treatments of PPD are in use but none has been able to remove the hyperpigmentation rapidly or completely. Though these treatment options may reduce the pigmentation, it tends to recur after stopping the treatment. As the systemic therapies may lead to a variety of adverse drug reactions, Q-switched Nd:YAG laser can be a safe and effective option in the treatment of PPD.

 

B) INTRODUCTION:

Pigmented purpuric dermatosis (PPD) is a group of diseases manifested as multiple petechial spots because of capillaritis. The underlying pathogenic mechanisms include mild degree of capillary inflammation and hemorrhage from the capillaries located in the papillary dermis [1].

RBC extravasation leads to purpuric spots. Hemosiderin-laden macrophages are at the root of hyperpigmentation, which is most often on the legs of the aged persons [2]. Various drugs and diseases like chronic venous hypertension, bezafibrate, acetaminophen, aspirin, diabetes mellitus etc. may be implicated in its pathogenesis [2] [3].

The most common type of PPD is Schamberg’s disease which has highest incidence in the middle-aged to elderly men. It often affects the lower legs. It is clinically characterized by yellow-brown patches having an oval to irregular margin. These patches may have pinpoint petechial spots [1].

The treatment of PPD is challenging. The currently available topical agents are topical corticosteroids along with moisturizers and topical calcineurin inhibitors like pimecrolimus 0.1%. The systemic agents that are being used are rutoside 50 mg BD, ascorbic acid 500 mg BD, pentoxifylline 400 mg BD, diosmin 450 mg/day, hesperidin 50 mg/day, euphorbia prostate extract 100 mg/day, calcium dobesilate 500 mg/day, colchicine 0.5 mg BD etc. [2] (BD= twice daily)

 

C) REVIEW OF LITERATURE:

Kim et al. found that the treatment options that are possibly effective are topical corticosteroids, oral antihistamines, pentoxifylline, ultraviolet phototherapy as first line therapy and colchicines, tetracycline as second line therapy [3].

According to study done by Spigariolo et al., the currently available topical agents are topical corticosteroids along with moisturizers and topical calcineurin inhibitors like pimecrolimus 0.1%. The systemic agents that can be efficacious are rutoside 50 mg BD, ascorbic acid 500 mg BD, pentoxifylline 300 mg/day or 400 mg BD, diosmin 450 mg/day, hesperidin 50 mg/day, euphorbia prostate extract 100 mg/day, calcium dobesilate 500 mg/day, colchicine 0.5 mg BD, griseofulvin 500-750 mg/day, cyclosporine 2-5 mg/kg/day etc. [2]. Whereas the topical agents are usually safe, the systemic agents can cause a variety of serious adverse drug reactions as well as drug interactions. These drawbacks are more complicated in nature and difficult to treat in the aged persons.

Different kinds of therapies have been suggested for the treatment of PPD which are as follows –

Phototherapy in the form of PUVA or NBUVB has been successfully used in some cases. Some reports suggest the use of pulse dye laser and non-ablative 1540 nm Er:YAG laser [2]. NBUVB is considered to be safer than PUVA. But, patient must be compliant to come on a regular basis for treatment, which is not possible for many patients; and especially when the treatment is given for long duration.

All the treatments already mentioned are either ineffective in the cases of PPD or the cases relapse after stopping the treatment. The hyperpigmentation seen in PPD is of cosmetic concern in many patients – it necessitates the use of some medications or therapies in reducing the pigmentation along with preventing its recurrence. Whereas the systemic agents can cause serious adverse drug reactions or are contraindicated in a few patients, the topical agents and laser therapy are expected to be devoid of the afore-mentioned disadvantages.

Though Q-switched Nd:YAG LASER has been used in the treatment of multiple disorders of hyperpigmentation like lentigines, freckles, dermal melanosis, melasma, dark lips, tattoo etc.; non-ablative akin resurfacing for wrinkles and acne scars; laser-assisted hair reduction, it has not been evaluated in the treatment of pigmented purpuric dermatosis. The known adverse effects are very few like immediate erythema, physical urticaria, acneiform eruption [4]. It is not contraindicated in patients having underlying systemic disease(s) or taking multiple medications.

So Q-switched Nd:YAG LASER can be a novel and unique mode of treating the hyperpigmentation of PPD.

There are a few studies on PPD both in India as well as globally. The number of studies on the treatment PPD is very few. So it urges the necessity of finding out a safe and effective treatment option for this cosmetically challenging condition.

 

 

 

MATERIALS AND METHODS:

A)    STUDY DESIGN: This will be an institution-based, Unicentric, randomised placebo-controlled split-limb trial.

B)    STUDY SETTING AND TIMELINES: The study will be conducted at Dermatology Outdoor of Bankura Sammilani Medical College & Hospital, a tertiary care hospital in Eastern India.

 

TIMELINE 

 

Timeline

Development of Case record form (CRF)  and questionnaires and validating the questionnaires in local language

Recruitment of patients, treatment administration, follow up and data collection

Data entry, analysis, report writing and submission

Dec 2023- Feb 2024

 

 

 

March 2024 - Sep 2024

 

 

 

 

Oct-Nov 2024

 

 

 

 

C)    PLACE OF STUDY: The study will be conducted at Dermatology Outpatient Department of Bankura Sammilani Medical College & Hospital.

 

D)    PERIOD OF STUDY: December 2023 to November 2024 (duration - 12 months) after obtaining Institutional Ethics Committee permission.

 

E)    STUDY POPULATION: All the adult patients having pigmented purpuric dermatosis bilaterally on the lower limbs, who have not received any treatment since 1 month.

F)     SAMPLE SIZE/DESIGN:

The estimated sample size is 20 (with 10 per group) because there are few trials on the treatment of PPD and most of the trials are outside India. The estimated sample size is based on the number of patients with PPD visiting dermatology OPD of BSMCH per year. As this will be a split-limb trial, total 10 patients will be recruited.

 

INCLUSION CRITERIA

·         Age more than 18 years to 80 years.

·         Pigmented purpuric dermatosis patients who have not received any treatment since 1 month.

·         Pigmentation present bilaterally on the lower limbs.

 

EXCLUSION CRITERIA

·         Pregnant and lactating women.

·         Patients having pigmented purpuric dermatosis at sites other than lower limbs.

·         Those having any skin disease other than pigmented purpuric dermatosis on the lower limb(s).

·         Patients with psychiatric disorders.

·         Participation in any clinical trial within the last 3 months.

·         Non-consenting patients

           

G)   RANDOMIZATION AND BLINDING:

Each limb of the eligible participants will be randomized into either group A (receiving Q-switched Nd:YAG LASER) or group B (receiving placebo).

Randomization will be done by a computer generated random number table using Winpepi software ETCETERA version 2.32 of WINPEPI (PEPI-for-Windows) program. Allocation concealment will be done by SNOSE (sequentially numbered opaque sealed envelope) technique.

Blinding: The study will be rendered participant-blind so the patients will be unaware of the difference in the treatment procedure between the two lower limbs – Nd:YAG laser on one limb and blank fire on the other limb.

 

H)    TREATMENT GROUPS:

            Each limb of the eligible participants will be randomized into -

                                i.            Group A (receiving Q-switched Nd:YAG LASER)

                              ii.            Group B (receiving placebo)

 

I)       STUDY VARIABLES:

1.      Demographic profile

2.      Serial digital imaging

3.      Biochemical and haematological parameters

4.      DLQI

5.      Skin Hyperpigmentation Index(SHI) score

6.      Cost of therapy

7.      Physicians and patients overall improvement score (Likert scale)

 

J)       DATA COLLECTION AND INTERPRETATION:

This study will be conducted after getting permission from Institutional Ethics Committee. All adult patients attending Dermatology OPD presenting with pigmented purpuric dermatosis will be included in the study based on inclusion and exclusion criteria. Proper written informed consent from each patient shall be obtained after explaining the study procedure in their own language.

 

 

 

K)   STUDY TOOLS:

·         Clinical history

·         General survey and systemic examination

·         Case record form (CRF)

·         Adverse effect checklist.

·         Complete hemogram (Hb, TC, DC, ESR, Platelets)

·         ICTC

·         Fasting blood sugar, urea, creatinine, liver function test

·         Digital camera

·         Pencil, rubber and pen

·         Q-switched Nd:YAG LASER machine (with all the equipments required)

·         EMLA (Eutectic mixture of local anaesthetics)

·         Moisturizers

 

L)  VISITS AND FOLLOW-UPS:


Baseline (0 weeks):

1.      The patients will be enrolled based on inclusion and exclusion criteria.

2.      Written informed consent will be obtained from the patients.

3.      All patients were referred to Integrated Counseling and Testing Centre (ICTC) and HIV status will be obtained.

4.      Randomization will be done.

5.      Detailed history taking and meticulous clinical examination will be done with reference to the hyperpigmentation.

6.      Laboratory parameters of routine hemogram, fasting blood glucose, serum urea, creatinine and liver function tests will be done.

7.      CRF will be filled.

8.      Photograph will be taken.

9.      EMLA will be applied 45 minutes prior to the procedure.

10.  Q-switched Nd:YAG laser with spot size 5, PRR (pulse repetition rate)=4 and fluence 600 mJ/pulse and placebo (blank fires) will be given according to randomization.

11.  SHI & DLQI calculated.

12.  The patients will be advised to come after 4 weeks.

 

1st follow-up (4 weeks):

1.      Photograph will be taken.

2.      EMLA will be applied 45 minutes prior to the procedure.

3.      According to randomization, Q-switched Nd:YAG laser with spot size 5, PRR (pulse repetition rate)=4 and fluence 800 mJ/pulse and placebo (blank fires)will be given.

4.      CRF will be filled.

5.      Any adverse events noted.

6.      The patients will be advised to come after 4 weeks.

 

2nd follow-up (8 weeks):

1.      Photograph will be taken.

2.      EMLA will be applied 45 minutes prior to the procedure.

3.      According to randomization, Q-switched Nd:YAG laser with spot size 5, PRR (pulse repetition rate)=4 and fluence 1000 mJ/pulse and placebo (blank fires)will be given.

4.      SHI & DLQI calculated in the 2nd follow-up.

5.      CRF will be filled.

6.      Any adverse events noted.

7.      The patients will be advised to come after 4 weeks.

 

3rd follow-up (12 weeks)/End of active treatment visit:

1.      Photograph will be taken.

2.      EMLA will be applied 45 minutes prior to the procedure.

3.      According to randomization, Q-switched Nd:YAG laser with spot size 5, PRR (pulse repetition rate)=4 and fluence 1200 mJ/pulse and placebo (blank fires)will be given.

4.      CRF will be filled.

5.      Any adverse events noted.

6.      The patients will be advised to come after 4 weeks.

 

4th follow-up (16 weeks)/Test of cure visit:

1.      SHI & DLQI calculated.

2.      CRF will be filled.

3.      Changes in laboratory values of routine hemogram, fasting blood glucose, serum urea, creatinine and liver function tests will be recorded.

4.      Any adverse events noted.

 

M)  TREATMENT PROCEDURES:

All eligible patients of pigmented purpuric dermatosis after inclusion and exclusion criteria, objective examination will be done and photograph of skin lesion of the patient will be taken for future comparison with next follow up. EMLA will be applied 120 minutes prior to the procedure. As per randomization, one lower limb of the patients will be treated with Q-switched Nd:YAG LASER at 1064 nm with spot size of 5 mm and PRR (pulse repetition rate) =4. Fluence of Q-Switched Nd:YAG is increased by 200 mJ/pulse in every session ( i.e. 600 mJ/pulse in first session, 800 mJ/pulse in 2nd session, 1000 mJ/pulse in 3rd session and 1200 mJ/pulse in 4th session). If patient can’t tolerate subsequent session and adverse reaction appears due to that fluence, the fluence used in previous session will be continued in the next session. The other lower limb will be treated with blank fire (placebo). Patients will be advised to apply moisturizers and sunscreen regularly. They will be asked to follow up every four weeks interval.

During every follow up patients will examined for any adverse effect and looked for improvement by comparing the lesion with previous photograph taken at baseline visit. SHI & DLQI will be calculated at baseline, 2nd& 4th follow-ups. A photograph will be taken again just before another session of Q-switched Nd:YAG LASER. And this procedure will be continued in all the session. Patient will be advised to use only sunscreen and emollients. Patient may be given symptomatic treatment according to any adverse effect.

                                                                                                            

N)  EFFECTIVENESS PARAMETERS:

The primary effectiveness parameter is the statistically-significant pigmentation reduction objectively calculated by skin hyperpigmentation index (SHI), in comparison with placebo.

 

O) SAFETY PARAMETERS:

Vital signs, spontaneously reported adverse events and those elicited by the clinician will be assessed at each follow-up. Changes in laboratory values of routine hemogram, fasting blood glucose, serum urea, creatinine and liver function tests will be recorded at baseline and 3rd follow-up.

 

P)  QUALITY OF LIFE PARAMETERS:

Quality of life in patients with trophic ulcer due to leprosy will be assessed by a validated vernacular (Bengali) version of Dermatology Life Quality Index (DLQI)[http://www.dermatology.org.uk/downloads/DLQI_Bengali.pdf], which consists of 10 questions, each scored between 0 and 3.

 

 

Q)  STATISTICAL ANALYSIS:

All the data will be put into Microsoft office Excel sheet and analyzed accordingly by using appropriate statistical software (med calc @ version of Ostend, Belgium).

 

OUTCOME DEFINITION:

The response to the treatment will be graded in to 5 categories. It is determined by Skin Hyperpigmentation Index (SHI).

Where SHI=Pigment score area with hyperpigmentation / pigment score of reference point.

1. Excellent response: Indicated by reduction of SHI by > 2.5.

2. Good Response: Indicated by reduction of SHI by 2 – 2.5.

3. Moderate Response: Indicated by reduction of SHI by 1.5 – 2.

4. Partial response: Indicated by reduction of SHI by 1 – 1.5.

5. Poor response: Indicated by reduction of SHI < 1.

 

ETHICAL CLEARANCE:

 

This study will be conducted after getting due permission from Institutional Ethics Committee. Proper written informed consent from each patient will be obtained after explaining the study procedure in their own language. The sample consent form in English, Hindi and Bengali are given below. 

 

 

 

 

 

 

WORK PLAN (ACTIVITY SCHEDULE OF RESEARCH WORK) 

1.      Preparation of research proposal-title & synopsis of research. 

 

2.      Literature review to aid in devising the aims and objectives of the study. 

 

3.      Formulation of statistical analysis plan and study sample & design education. 

 

4.      Obtaining ethical & other necessary clearances from requisite authorities. 

 

5.      Preparation of patient information and consent forms. 

 

6.      Starting the data collection once the research proposal is approved. 

 

7.      Completing the data collection and analysis within the stipulated time frame of 12 months after approval of research proposal by the IEC. 

 

8.      Reporting and managing any adverse events during the period of study. 

 

9.      After completing statistical analysis, evaluation of obtained results and observations and the significance of the studyà completing the discussion and concluding the study. 

 

10.  Final submission of the research work within stipulated time frame to IEC and peer reviewed journal.

 

REFERNCES:

1)      WarrenW.Piette.Purpura: Mechanisms and Differential diagnosis. In: Jean L. Bolognia (ed). Dermatology. 4th edition. China: ELSEVIER;2018.385-6

 

2)      Spigariolo CB, Giacalone S, Nazzaro G. Pigmented Purpuric Dermatoses: A Complete Narrative Review. J Clin Med. 2021 May 25;10(11):2283.

3)      Kim KE, Moon HR, Ryu HJ. Dermoscopic Findings and the Clinicopathologic Correlation of Pigmented Purpuric Dermatosis: A Retrospective Review of 60 Cases. Ann Dermatol. 2021 Jun;33(3):214–21.

4)      Goel A. Clinical applications of Q-switched NdYAG laser. Indian J Dermatol Venereol Leprol. 2008;74(6):682–6.

5)      Schober SM, Peitsch WK, Bonsmann G, Metze D, Thomas K, Goerge T, et al. Early treatment with rutoside and ascorbic acid is highly effective for progressive pigmented purpuric dermatosis. J Dtsch Dermatol Ges J Ger Soc Dermatol JDDG. 2014 Dec;12(12):1112–9.

 
 
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