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Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

Primary Purpose

Chronic Rhinosinusitis (Diagnosis)

Status

Recruiting

Phase

Not Applicable

Locations

Australia

Study Type

Interventional

Intervention

Microbiome Transplant

Placebo

About this trial

This is an interventional treatment trial for Chronic Rhinosinusitis (Diagnosis) focused on measuring microbiota, transplant, paranasal sinuses, nasal lavage

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria (patient):

Diagnosis of Chronic Rhinosinusitis as defined by the presence of 2 or more major sinonasal symptoms (nasal blockage, nasal discharge, loss of smell, and facial pain/ fullness) for a minimum of 12 weeks
Endoscopic confirmation of middle meatus inflammation or presence of mucopurulence, and /or CT confirmation of paranasal sinus inflammation.
Previous nasal surgery with patent ostia to the diseased ethmoids and maxillary sinuses
Signed written informed consent

Inclusion criteria (donor):

No history of sinonasal or lower airway disease for the last 2 years other than the common cold.
No clinical findings of sinonasal disease at the inclusion visit.
Accepted as a donor by the patient.
Signed informed consent to participate in the study.

Exclusion Criteria:

Exclusion criteria (patient):

Aged <18 or >70 years
Allergy to amoxicillin or clavulanate potassium and Clarithromycin.
Nasal polyposis
Antibiotic treatment in the last 4 weeks
Patients with a history supporting a diagnosis of immune deficiency will be tested (Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG) and IgG subclasses, MBL) and /or are immunocompromised due to disease and / or medication ( e.g., insulin dependent diabetes mellitis, systemic corticosteroids)
Patients who live with someone who is severly immunocompromised.
Patients with cystic fibrosis or ciliary dyskinesia
Patients who have been on an active investigational therapy within 2 months of screening
Patients who have clinically significant laboratory abnormalities
Patients who are pregnant, breast feeding or planning to become pregnant during the study
Patients who are not willing to use a double barrier method of contraception during the study that is:-
1. females must use contraceptive pill or Intra-uterine device (IUD) or similar and condoms
2. males must use condoms and spermicidal gel
Patients currently on any medication that may affect the results in an unpredictable manner
The patient does not agree to comply with or is unable to meet all study requirements for the duration of the study period
Patients deemed by the investigator to be unsuitable for participation in the study
Patients who have had Coronavirus-19 (COVID-19) within the last 2 months.

Exclusion criteria (donor):

Findings in the prestudy pathogen scan that makes the donor unsuitable. Prestudy pathogen scan: Prior to first donation, the donors will be tested for HIV, Human T-lymphotropic virus 1 and 2, Hepatitis B and C, Syphilis, Tuberculosis, Herpes Simplex (HSV 1 and 2), Varicella Zoster (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Methicillin-resistant Staphylococcus aureus (MRSA) and a standard panel for sinonasal pathogens (Pneumococci, H. Influenza, Beta-streptococci and M. Catarrhalis).
Donors who have had COVID-19 within the last 2 months.
If the donor is positive for Herpes Simplex, CMV or EBV they will be considered unsuitable as a donor for a patient negative for the same pathogen. If the donor is positive for any other pathogen they will be considered unsuitable as a donor entirely.

Sites / Locations

Royal Brisbane and Women's HospitalRecruiting
University of Queensland
Monash Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Control

Arm Description

For each nostril, the donated nasal wash sample is quiesced to 15 mls with saline Nasal Microbiota Transplant therapy.

For each nostril, 15 mls of saline will be used as the placebo therapy.

Outcomes

Primary Outcome Measures

Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire

Change of burden of disease as measured by the SNOT-22 (22 item sinonasal outcome test) questionnaire in patients. Each item graded 0-5. Minimum score 0, Maximum 105 Interpretation: Higher score indicates poorer disease control.

Secondary Outcome Measures

Lund-Kennedy endoscopic assessment score

Change of grading of disease severity using the Lund-Kennedy endoscopy score based on clinical assessment of the middle meatus. 4-item criteria, with score of 0-2 Minimum score: 0, Maximum 8 Interpretation: Higher score indicates a higher degree of disease severity based on clinical assessment.

Characterisation of nasal microbiome in study participants

Change in nasal microbiome associated with clinical outcomes such as decrease in presence, absence or abundance of bacterial pathogens.

Characterisation of microbiome within effective donors as compared to ineffective donors

Analysis of microbes (bacterial strains, viruses and fungi), and human cell types within donor specimens.

Adverse events of Participating Patients

Any adverse event

Cytokine level - Interleukin 5 or (IL-5)

Change of lL-5 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interleukin 13 (IL-13)

Change of lL-13 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interleukin 2 (IL-2)

Change of lL-2 in nasal secretion/swab markers across duration of study. Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interleukin 6 (IL-6)

Change of lL-6 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interleukin 10 (IL-10)

Change of lL-10 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interferon gamma (IFN-γ)

Change of IFN-Y in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Cytokine level - Interleukin 4 (IL-4)

Change of IL-4 in nasal secretion/swab markers across duration of study.Each cytokine will be quantified using a highly sensitive immunoassay which will use biotinylated antibodies specific to each cytokine to bind the cytokine molecules in the sample. Interactions measured on a flow cytometer and compared against its relevant standard. this will result in a measure of the total concentration of the cytokine in the sample (pg/ml).

Full Information

NCT ID

NCT05400616

First Posted

May 12, 2022

Last Updated

November 10, 2022

Sponsor

The University of Queensland

Collaborators

Royal Brisbane and Women's Hospital, Monash Health, Queensland University of Technology

1. Study Identification

Unique Protocol Identification Number

NCT05400616

Brief Title

Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

Official Title

Phase-II Randomized Control Trial of Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 10, 2022 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Queensland

Collaborators

Royal Brisbane and Women's Hospital, Monash Health, Queensland University of Technology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Chronic Rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal passage and paranasal sinuses that places significant burden on affected patients and global healthcare systems. Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory. Recently, the theory of a damaged microbiome (dysbiosis) as a cause or promoting factor behind CRS has gained increasing evidence from the scientific community. A condition of the gut with microbial dysbiosis (c.difficile) has previously employed microbiota transplant treatment with great success in long-term health outcomes. Such treatments are shown to repopulate bacterial microenvironment and restore protective commensal bacterial load. A pilot study conducted by this study team trialed a novel intervention of a Nasal Microbiota Transplant in a small group of participants. Preliminary results suggested significantly improved CRS symptoms after treatment with a healthy donor microbiota transplant, compared to the pre-transplant baseline. The addition of a randomized-control trial with inclusion of a placebo group is the next step. In this study, investigators aim to perform a two-arm, double-blinded, phase II randomized controlled clinical trial in order to assess the efficacy of a Nasal Microbiota Transplant against a placebo in a cohort of CRS patients without Nasal Polyps (CRSsNP).

Detailed Description

Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory. A microbiota therapy, as an alternative treatment to antibiotics, has the potential of improving outcomes for CRS patients long-term, whilst reducing the use of antibiotics in the community. Several attempts of studies to define the role of microbiota of the nose and paranasal sinuses in health and disease have not yet been able to achieve a universal consensus. This is in part due to the significant inter-individual microbiota variation and complexity within humans. Such challenges have also limited the use of probiotic assemblages of one or a combination of few bacterial species in treatment of CRS. The data derived from this study will add to our understanding of the role of the microbiome in the airways and its role in interfering with respiratory pathogens and host immunity. This is likely to have implications for CRS microbiome-based therapies, and also other potentially related respiratory conditions such as asthma, and chronic obstructive pulmonary disease (COPD). In this study, investigators will recruit patients suffering from chronic rhinosinusitis without polyps (CRSsNP) and healthy participants that do not have a history of sinonasal disease. The sinus microbiome transplants will occur over a 2 week period, with regular follow up for up to 6-months post intervention. Main outcomes include change in disease severity, symptom severity, inflammatory changes, and microbial composition across the study period. Successful results from this trial may pave the way for a novel therapeutic for CRS patients. This study has received ethics approval from the Royal Brisbane and Women's Health Human Resource and Ethics Committee (RBWH HREC).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Rhinosinusitis (Diagnosis)

Keywords

microbiota, transplant, paranasal sinuses, nasal lavage

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Eligible patient participants will be randomly assigned to intervention or control group (1:1 ratio) as per a computer-generated randomisation schedule using permuted blocks of random sizes. The block sizes will not be disclosed, to ensure concealment. Both groups will receive two weeks of antibiotic treatment between recruitment and allocation to a study arm. The study team will work with each patient participant to find a suitable donor. Some patient participants will prefer a donor that is known to them other patients will prefer a donor that is an unknown volunteer. Potential donors who consent to participating in this study will be screened and be classified as donor-participants in the study.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

A biostatistician, not involved in assignment or care of the trial participants, will generate the randomisation sequence with a computerised random number generator. A research assistant, not involved in any other aspect of this study, will place the assigned treatments into sealed envelopes. Participants (Patients and donors) will be blinded from knowing if they are in the intervention group or the control group. The nurse and doctors attending to the participants will also be blinded. A member of the study team who will prepare the Nasal Microbiota Transplant therapy will not be masked. The person doing the analysis will be masked.

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

For each nostril, the donated nasal wash sample is quiesced to 15 mls with saline Nasal Microbiota Transplant therapy.

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

For each nostril, 15 mls of saline will be used as the placebo therapy.

Intervention Type

Procedure

Intervention Name(s)

Microbiome Transplant

Intervention Description

A raw microbiome, is collected from a donor without any sinonasal health problems, as a nasal lavage.

Intervention Type

Procedure

Intervention Name(s)

Placebo

Intervention Description

Normal saline.

Primary Outcome Measure Information:

Title

Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire

Description

Time Frame

Week 1 (Day 1) to Week 20

Secondary Outcome Measure Information:

Title

Lund-Kennedy endoscopic assessment score

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Characterisation of nasal microbiome in study participants

Description

Change in nasal microbiome associated with clinical outcomes such as decrease in presence, absence or abundance of bacterial pathogens.

Time Frame

Week 1 (Day 1) to Week 20

Title

Characterisation of microbiome within effective donors as compared to ineffective donors

Description

Analysis of microbes (bacterial strains, viruses and fungi), and human cell types within donor specimens.

Time Frame

Week 1 (Day 1) - Week 2 (Day 9)

Title

Adverse events of Participating Patients

Description

Any adverse event

Time Frame

From the day participating patients give signed consent (2-4 weeks before baseline) until the day of their End of study visit (Up to 33 weeks).

Title

Cytokine level - Interleukin 5 or (IL-5)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interleukin 13 (IL-13)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interleukin 2 (IL-2)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interleukin 6 (IL-6)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interleukin 10 (IL-10)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interferon gamma (IFN-γ)

Description

Time Frame

Week 1 (Day 1) to Week 20

Title

Cytokine level - Interleukin 4 (IL-4)

Description

Time Frame

Week 1 (Day 1) to Week 20

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria (patient): Diagnosis of Chronic Rhinosinusitis as defined by the presence of 2 or more major sinonasal symptoms (nasal blockage, nasal discharge, loss of smell, and facial pain/ fullness) for a minimum of 12 weeks Endoscopic confirmation of middle meatus inflammation or presence of mucopurulence, and /or CT confirmation of paranasal sinus inflammation. Previous nasal surgery with patent ostia to the diseased ethmoids and maxillary sinuses Signed written informed consent Inclusion criteria (donor): No history of sinonasal or lower airway disease for the last 2 years other than the common cold. No clinical findings of sinonasal disease at the inclusion visit. Accepted as a donor by the patient. Signed informed consent to participate in the study. Exclusion Criteria: Exclusion criteria (patient): Aged <18 or >70 years Allergy to amoxicillin or clavulanate potassium and Clarithromycin. Nasal polyposis Antibiotic treatment in the last 4 weeks Patients with a history supporting a diagnosis of immune deficiency will be tested (Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG) and IgG subclasses, MBL) and /or are immunocompromised due to disease and / or medication ( e.g., insulin dependent diabetes mellitis, systemic corticosteroids) Patients who live with someone who is severly immunocompromised. Patients with cystic fibrosis or ciliary dyskinesia Patients who have been on an active investigational therapy within 2 months of screening Patients who have clinically significant laboratory abnormalities Patients who are pregnant, breast feeding or planning to become pregnant during the study Patients who are not willing to use a double barrier method of contraception during the study that is:- females must use contraceptive pill or Intra-uterine device (IUD) or similar and condoms males must use condoms and spermicidal gel Patients currently on any medication that may affect the results in an unpredictable manner The patient does not agree to comply with or is unable to meet all study requirements for the duration of the study period Patients deemed by the investigator to be unsuitable for participation in the study Patients who have had Coronavirus-19 (COVID-19) within the last 2 months. Exclusion criteria (donor): Findings in the prestudy pathogen scan that makes the donor unsuitable. Prestudy pathogen scan: Prior to first donation, the donors will be tested for HIV, Human T-lymphotropic virus 1 and 2, Hepatitis B and C, Syphilis, Tuberculosis, Herpes Simplex (HSV 1 and 2), Varicella Zoster (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Methicillin-resistant Staphylococcus aureus (MRSA) and a standard panel for sinonasal pathogens (Pneumococci, H. Influenza, Beta-streptococci and M. Catarrhalis). Donors who have had COVID-19 within the last 2 months. If the donor is positive for Herpes Simplex, CMV or EBV they will be considered unsuitable as a donor for a patient negative for the same pathogen. If the donor is positive for any other pathogen they will be considered unsuitable as a donor entirely.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anders Cervin, MD,FRACS

Phone

617 3497 3588

a.cervin@uq.edu.au

First Name & Middle Initial & Last Name or Official Title & Degree

Diane Maresco-Pennisi, PhD

Phone

617 3346 6072

d.marescopennisi@uq.edu.au

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anders Cervin, MD,FRACS

Organizational Affiliation

University of Queensland/Royal Brisbane and Women's Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Royal Brisbane and Women's Hospital

City

Brisbane

State/Province

Queensland

ZIP/Postal Code

4006

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Abigail Walker, MD,FRACS

abiwalker@doctors.org.uk

Facility Name

University of Queensland

City

Brisbane

State/Province

Queensland

ZIP/Postal Code

4680

Country

Australia

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Diane Maresco-Pennisi, PhD

d.marescopennisi@uq.edu.au

First Name & Middle Initial & Last Name & Degree

Joshua Liaw, MBBS (Hons)

First Name & Middle Initial & Last Name & Degree

Anders Cervin, MDPHD FRACS

First Name & Middle Initial & Last Name & Degree

Diane Maresco-Pennisi, PhD

First Name & Middle Initial & Last Name & Degree

Flavia Huygens, PhD

First Name & Middle Initial & Last Name & Degree

Jo Rimmer, MD FRACS MA (Hons)

First Name & Middle Initial & Last Name & Degree

Zhen Liu, MD

First Name & Middle Initial & Last Name & Degree

Abigail Walker, MD FRACS

Facility Name

Monash Health

City

Melbourne

Country

Australia

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

JoAnne Rimmer, MD,FRACS

joanne.rimmer@monashhealth.org

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

There may be a possibility to share deidentified individual outcome data upon request, if the request is in accordance with the privacy statements of this study.

Citations:

PubMed Identifier

31879084

Citation

Marsh RL, Aho C, Beissbarth J, Bialasiewicz S, Binks M, Cervin A, Kirkham LS, Lemon KP, Slack MPE, Smith-Vaughan HC. Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures. Int J Pediatr Otorhinolaryngol. 2020 Mar;130 Suppl 1(Suppl 1):109836. doi: 10.1016/j.ijporl.2019.109836. Epub 2019 Dec 18.

Results Reference

background

PubMed Identifier

32278449

Citation

Cho DY, Hunter RC, Ramakrishnan VR. The Microbiome and Chronic Rhinosinusitis. Immunol Allergy Clin North Am. 2020 May;40(2):251-263. doi: 10.1016/j.iac.2019.12.009. Epub 2020 Jan 16.

Results Reference

background

PubMed Identifier

28785927

Citation

Psaltis AJ, Wormald PJ. Therapy of Sinonasal Microbiome in CRS: A Critical Approach. Curr Allergy Asthma Rep. 2017 Sep;17(9):59. doi: 10.1007/s11882-017-0726-x.

Results Reference

background

PubMed Identifier

22469599

Citation

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1-12. doi: 10.4193/Rhino12.000.

Results Reference

background

PubMed Identifier

26510171

Citation

Mahdavinia M, Keshavarzian A, Tobin MC, Landay AL, Schleimer RP. A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS). Clin Exp Allergy. 2016 Jan;46(1):21-41. doi: 10.1111/cea.12666.

Results Reference

background

PubMed Identifier

12580880

Citation

Buckland JR, Thomas S, Harries PG. Can the Sino-nasal Outcome Test (SNOT-22) be used as a reliable outcome measure for successful septal surgery? Clin Otolaryngol Allied Sci. 2003 Feb;28(1):43-7. doi: 10.1046/j.1365-2273.2003.00663.x.

Results Reference

background

PubMed Identifier

28337570

Citation

Rudmik L. Economics of Chronic Rhinosinusitis. Curr Allergy Asthma Rep. 2017 Apr;17(4):20. doi: 10.1007/s11882-017-0690-5.

Results Reference

background

PubMed Identifier

27902866

Citation

Wagner Mackenzie B, Waite DW, Hoggard M, Douglas RG, Taylor MW, Biswas K. Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis. Environ Microbiol. 2017 Jan;19(1):381-392. doi: 10.1111/1462-2920.13632. Epub 2017 Jan 18.

Results Reference

background

Links:

URL

https://clinicaltrials.gov/ct2/show/NCT03122795

Description

Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP) - pilot study

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Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)

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