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Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: Study protocol for the MACRO randomised controlled trial

Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: Study protocol for the MACRO randomised controlled trial
Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: Study protocol for the MACRO randomised controlled trial

Background: Chronic rhinosinusitis (CRS) is a common source of ill health; 11% of UK adults reported CRS symptoms in a worldwide population study. Guidelines are conflicting regarding whether antibiotics should be included in primary medical management, reflecting the lack of evidence in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiveness of endoscopic sinus surgery (ESS) or a prolonged course of antibiotics (clarithromycin) in adult patients with CRS in terms of symptomatic improvement and costs to the National Health Service compared with standard medical care (intranasal medication) at 6 months. Methods/design: A three-arm parallel-group trial will be conducted with patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care). They will be randomised to receive: (1) intranasal medication plus ESS, (2) intranasal medication plus clarithromycin (250 mg) or (3) intranasal medication plus a placebo. Intranasal medication (current standard medical care) is defined as a spray or drops of intranasal corticosteroids and saline irrigations. The primary outcome measure is the SNOT-22 questionnaire, which assesses disease-specific health-related quality of life. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted in at least 16 secondary or tertiary care centres with an internal pilot at six sites for 6 months. Discussion: The potential cardiovascular side effects of macrolide antibiotics have been recently highlighted. The effectiveness of antibiotics will be established through this trial, which may help to reduce unnecessary usage and potential morbidity. If ESS is shown to be clinically effective and cost-effective, the trial may encourage earlier intervention. In contrast, if it is shown to be ineffective, then there should be a significant reduction in surgery rates. The trial results will feed into the other components of the MACRO research programme to establish best practice for the management of adults with CRS and design the ideal patient pathway across primary and secondary care. Trial registration: ISRCTN36962030. Registered on 17 October 2018.

chronic rhinosinusitis, clarithromycin, endoscopic sinus surgery, randomised controlled trial
1745-6215
Philpott, Carl
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Le Conte, Steffi
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Beard, David
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Cook, Jonathan
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Sones, William
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Morris, Steve
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Clarke, Caroline S.
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Thomas, Mike
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Little, Paul
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Vennik, Jane
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Lund, Valerie
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Blackshaw, Helen
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Schilder, Anne
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Durham, Stephen
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Denaxas, Spiros
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Carpenter, James
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Boardman, James
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Hopkins, Claire
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Med, Neil
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Boland, Keith
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Woods, Jane
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Ferreira, Teresa
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Philpott, Carl
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Le Conte, Steffi
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Beard, David
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Cook, Jonathan
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Sones, William
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Morris, Steve
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Clarke, Caroline S.
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Thomas, Mike
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Little, Paul
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Vennik, Jane
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Lund, Valerie
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Blackshaw, Helen
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Schilder, Anne
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Durham, Stephen
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Denaxas, Spiros
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Carpenter, James
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Boardman, James
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Hopkins, Claire
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Med, Neil
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Boland, Keith
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Woods, Jane
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Ferreira, Teresa
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Philpott, Carl, Le Conte, Steffi, Beard, David, Cook, Jonathan, Sones, William, Morris, Steve, Clarke, Caroline S., Thomas, Mike, Little, Paul, Vennik, Jane, Lund, Valerie, Blackshaw, Helen, Schilder, Anne, Durham, Stephen, Denaxas, Spiros, Carpenter, James, Boardman, James, Hopkins, Claire, Med, Neil, Boland, Keith, Woods, Jane and Ferreira, Teresa (2019) Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: Study protocol for the MACRO randomised controlled trial. Trials, 20 (1), [246]. (doi:10.1186/s13063-019-3314-7).

Record type: Article

Abstract

Background: Chronic rhinosinusitis (CRS) is a common source of ill health; 11% of UK adults reported CRS symptoms in a worldwide population study. Guidelines are conflicting regarding whether antibiotics should be included in primary medical management, reflecting the lack of evidence in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiveness of endoscopic sinus surgery (ESS) or a prolonged course of antibiotics (clarithromycin) in adult patients with CRS in terms of symptomatic improvement and costs to the National Health Service compared with standard medical care (intranasal medication) at 6 months. Methods/design: A three-arm parallel-group trial will be conducted with patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care). They will be randomised to receive: (1) intranasal medication plus ESS, (2) intranasal medication plus clarithromycin (250 mg) or (3) intranasal medication plus a placebo. Intranasal medication (current standard medical care) is defined as a spray or drops of intranasal corticosteroids and saline irrigations. The primary outcome measure is the SNOT-22 questionnaire, which assesses disease-specific health-related quality of life. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted in at least 16 secondary or tertiary care centres with an internal pilot at six sites for 6 months. Discussion: The potential cardiovascular side effects of macrolide antibiotics have been recently highlighted. The effectiveness of antibiotics will be established through this trial, which may help to reduce unnecessary usage and potential morbidity. If ESS is shown to be clinically effective and cost-effective, the trial may encourage earlier intervention. In contrast, if it is shown to be ineffective, then there should be a significant reduction in surgery rates. The trial results will feed into the other components of the MACRO research programme to establish best practice for the management of adults with CRS and design the ideal patient pathway across primary and secondary care. Trial registration: ISRCTN36962030. Registered on 17 October 2018.

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Accepted/In Press date: 21 March 2019
Published date: 29 April 2019
Keywords: chronic rhinosinusitis, clarithromycin, endoscopic sinus surgery, randomised controlled trial

Identifiers

Local EPrints ID: 431470
URI: http://eprints.soton.ac.uk/id/eprint/431470
ISSN: 1745-6215
PURE UUID: 66326a91-3429-4f2f-8b75-c11a1a25c633
ORCID for Paul Little: ORCID iD orcid.org/0000-0003-3664-1873
ORCID for Jane Vennik: ORCID iD orcid.org/0000-0003-4602-9805

Catalogue record

Date deposited: 05 Jun 2019 16:30
Last modified: 12 Jul 2024 01:57

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Contributors

Author: Carl Philpott
Author: Steffi Le Conte
Author: David Beard
Author: Jonathan Cook
Author: William Sones
Author: Steve Morris
Author: Caroline S. Clarke
Author: Mike Thomas
Author: Paul Little ORCID iD
Author: Jane Vennik ORCID iD
Author: Valerie Lund
Author: Helen Blackshaw
Author: Anne Schilder
Author: Stephen Durham
Author: Spiros Denaxas
Author: James Carpenter
Author: James Boardman
Author: Claire Hopkins
Author: Neil Med
Author: Keith Boland
Author: Jane Woods
Author: Teresa Ferreira

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