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Abstract
Objective A multicentre, randomised non-inferiority trial compared the efficacy and safety of 14 days of ofloxacin and metronidazole (standard-of-care (SoC)) versus a single dose of intramuscular ceftriaxone followed by 5 days of azithromycin and metronidazole (intervention arm (IA)) in women with mild-to-moderate pelvic inflammatory disease (PID).
Methods Women with a clinical diagnosis of PID presenting at sexual health services were randomised to the SoC or IA arms. Treating clinicians and participants were not blinded to treatment allocation but the clinician performing the assessment of primary outcome was blinded. The primary outcome was clinical cure defined as ≥70% reduction in the modified McCormack pain score at day 14–21 after starting treatment. Secondary outcomes included adherence, tolerability and microbiological cure.
Results Of the randomised population 72/153 (47.1%) reached the primary end point in the SoC arm, compared with 68/160 (42.5%) in the IA (difference in cure 4.6% (95% CI −15.6% to 6.5%). Following exclusion of 86 women who were lost to follow-up, attended outside the day 14–21 follow-up period, or withdrew consent, 72/107 (67.3%) had clinical cure in the SoC arm compared with 68/120 (56.7%) in the IA, giving a difference in cure rate of 10.6% (95% CI −23.2% to 1.9%). We were unable to demonstrate non-inferiority of the IA compared with SoC arm. Women in the IA took more treatment doses compared with the SoC group (113/124 (91%) vs 75/117 (64%), p=0.0001), but were more likely to experience diarrhoea (61% vs 24%, p<0.0001). Of 288 samples available for analysis, Mycoplasma genitalium was identified in 10% (28/288), 58% (11/19) of which had baseline antimicrobial resistance-associated mutations.
Conclusion A short-course azithromycin-based regimen is likely to be less effective than the standard treatment with ofloxacin plus metronidazole. The high rate of baseline antimicrobial resistance supports resistance testing in those with M. genitalium infection to guide appropriate therapy.
Trial registration number 2010-023254-36.
- pelvic inflammatory disease
- azithromycin
- mycoplasma
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Footnotes
Handling editor Jane S Hocking
Twitter @GillianDean6, @suneeta_soni_
Collaborators Trial co-ordinators: Marie Hyslop, Gemma Sugar, Amy Arbon, Jane Cox; Brighton & Sussex University Hospitals NHS Trust (BSUH): Louise Kerr, Sarah Kirk, Marion Campbell, Anthony Kelly; University Hospitals Birmingham NHS Foundation Trust: Jan Harding, Monika Okriak; Imperial College Healthcare NHS Trust: Linda Greene, Wilbert Ayap; St George's University Hospitals NHS Trust: Phil Hay, Olonike Okolo; Homerton University Hospital: Iain Reeves, Sifiso Mguni; Charing Cross Hospital, Imperial College Healthcare NHS Trust: Michael Rayment, Kribashnie Nundlall; Sheffield Teaching Hospitals NHS Foundation Trust: Gill Dilke-Wing, Charlie Sayer; Eastbourne District General Hospital, Conquest Hospital, East Sussex Healthcare NHS Trust: Kazeem Aderogba, Harish Patel; Queen Elizabeth Hospital, Woolwich: Judith Russell; Trial sponsors/BSUH R&D Department: Scott Harfield, Nicky Perry; Public Health England: Sarah Alexander, Michelle Cole, Catherine Ison; Advisory board: Janet Wilson, Jonathan Ross, Peter Greenhouse, Catherine Ison, Jackie Ross; Behaviour Medicine: Rob Horne; DSMB: Martin Fisher, Stephanie Goubet, Scott Harfield; helpful comments on the manuscript drafts: Paddy Horner.
Contributors GD, SS, JW were involved in the design and writing the manuscript. GD and JW were involved in conducting the study. CS was involved in the study design and performed the statistical analysis, as well as reviewing the manuscript. RP conducted Mycoplasma genitalium tests and reviewed the manuscript. JR advised on the conduct of the study and revised the manuscript before submission.
Funding Funding for this trial was provided by the NIHR Research for Patient Benefit programme (award reference number PB-PG-0609–19279).
Disclaimer This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB- PG-0609–19279). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Competing interests JR reports personal fees from GSK Pharma, Hologic Diagnostics, Mycovia and Janssen Pharma as well as ownership of shares in GSK Pharma and AstraZeneca Pharma; and is author of the UK and European Guidelines on Pelvic Inflammatory Disease; is a Member of the European Sexually Transmitted Infections Guidelines Editorial Board; is a Member of the National Institute for Health Research Funding Committee (Health Technology Assessment programme); was previously a Member of the National Institute for Health Research HTA Primary Care, Community and Preventative Interventions Panel (2013-2016). He is an NIHR Journals Editor and associate editor of Sexually Transmitted Infections journal. He is an officer of the British Association for Sexual Health and HIV (vice-president), and the International Union against Sexually Transmitted Infections (treasurer), and a charity trustee of the Sexually Transmitted Infections Research Foundation.
Patient consent for publication Not required.
Ethics approval The study protocol was approved by Brighton & Sussex University Hospitals NHS Trust ethics committee (EC Reference Number: 10/H1107/70). Written informed consent was obtained from participants.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data (de-identified participant data) and statistical analysis plans are held by the trial statistician c.sabin@ucl.ac.uk. https://orcid.org/0000-0001-5173-2760. The authors have added the data tables as supplementary information. The trial protocol is available on request.