Prophylactic antibiotics for the prevention of infection following operative vaginal delivery (ANODE): study protocol for a randomised controlled trial

Knight, Marian; Mottram, Linda; Gray, Sir Muir; Partlett, Christopher; Juszczak, Ed

doi:10.1186/s13063-018-2787-0

Cited by 7 publications

(7 citation statements)

References 16 publications

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“…In the context of increasing concerns around the unnecessary use of antibiotics, and their implications for antimicrobial resistance [11] and allergic conditions [12], it is vital that these decisions are evidencebased. The ANODE trial, a multi-centre, blinded, placebo-controlled trial from the UK, is due to report findings from 3,424 women in 2019, and will be the largest study to date of antibiotic prophylaxis following OVD [13]. This review will cover:…”

Section: Introductionmentioning

confidence: 99%

Operative vaginal delivery and post-partum infection

Mohamed-Ahmed

Hinshaw

Knight

2019

Best Practice & Research Clinical Obstetrics & Gynaecol

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Over the past decade, there has been an increase in awareness of infections associated with pregnancy and delivery. The most significant cause of postpartum infection is caesarean section, with 20-25% of operations followed by wound infections, endometritis or urinary tract infections. Around 13% of women in the UK undergo operative vaginal delivery (OVD) with forceps or vacuum, which is also associated with an increased risk of infection, estimated at 0.7% to 16% of these deliveries. Despite this, previous reviews have identified only one small trial of antibiotic prophylaxis in 393 women, and concluded that there was insufficient evidence to support the routine use of prophylactic antibiotics after operative vaginal delivery. The ANODE trial, a multi-centre, blinded, placebocontrolled trial from the UK, is due to report findings from more than 3,400 women in 2019, and will be the largest study to date of antibiotic prophylaxis following operative vaginal delivery.

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Section: Introductionmentioning

confidence: 99%

Operative vaginal delivery and post-partum infection

Mohamed-Ahmed

Hinshaw

Knight

2019

Best Practice & Research Clinical Obstetrics & Gynaecol

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“…The ANODE trial was a multicentre, randomised, blinded, controlled trial done at 27 hospital obstetric units in the UK. The trial protocol has been published previously 18 and the full protocol is available in the appendix. Women who had undergone forceps or vacuum delivery at 36 weeks or greater gestation, with no indication for ongoing prescription of antibiotics in the post-partum period and no contraindications to prophylactic amoxicillin and clavulanic acid, were randomly assigned (1:1) to receive a single intravenous dose of prophylactic amoxicillin and clavulanic acid or placebo.…”

Section: Methodsmentioning

confidence: 99%

Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial

et al. 2019

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Summary Background Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth. Methods In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual. Findings Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49–0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment. Interpretation This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this. Funding NIHR Health Technology Assessment programme.

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“…Of these women, around 200 will be diagnosed with severe infection 7 and up to four may die from their infection. 28 There is, therefore, considerable scope for direct patient benefit from an effective preventative strategy. Other non-randomised studies suggest higher infection rates of up to 16%, 29 which would correspondingly lead to an even greater potential benefit from a preventative therapy.…”

Section: Fundingmentioning

confidence: 99%

“…T he trial protocol 28 and results 30 have been previously published and parts of the published articles are reproduced throughout this report. These have been reproduced with permission from Knight et al 28 [This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.]…”

Section: Objectivementioning

confidence: 99%

“…To ensure that awareness of allocation could not influence outcomes, it was specified that the research nurse/midwife conducting telephone follow-up should not have prepared or checked the intervention. 28 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.…”

Section: Interventionmentioning

confidence: 99%

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Intravenous co-amoxiclav to prevent infection after operative vaginal delivery: the ANODE RCT

Knight

Chiocchia

Partlett

et al. 2019

Health Technol Assess

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Background Sepsis is a leading cause of direct and indirect maternal death in both the UK and globally. All forms of operative delivery are associated with an increased risk of sepsis, and the National Institute for Health and Care Excellence’s guidance recommends the use of prophylactic antibiotics at all caesarean deliveries, based on substantial randomised controlled trial evidence of clinical effectiveness. A Cochrane review, updated in 2017 (Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Antibiotic prophylaxis for operative vaginal delivery. Cochrane Database Syst Rev 2017;8:CD004455), identified only one small previous trial of prophylactic antibiotics following operative vaginal birth (forceps or ventouse/vacuum extraction) and, given the small study size and extreme result, suggested that further robust evidence is needed. Objectives To investigate whether or not a single dose of prophylactic antibiotic following operative vaginal birth is clinically effective for preventing confirmed or presumed maternal infection, and to investigate the associated impact on health-care costs. Design A multicentre, randomised, blinded, placebo-controlled trial. Setting Twenty-seven maternity units in the UK. Participants Women who had an operative vaginal birth at ≥ 36 weeks’ gestation, who were not known to be allergic to penicillin or constituents of co-amoxiclav and who had no indication for ongoing antibiotics. Interventions A single dose of intravenous co-amoxiclav (1 g of amoxicillin/200 mg of clavulanic acid) or placebo (sterile saline) allocated through sealed, sequentially numbered, indistinguishable packs. Main outcome measures Primary outcome – confirmed or suspected infection within 6 weeks of giving birth. Secondary outcomes – severe sepsis, perineal wound infection, perineal pain, use of pain relief, hospital bed stay, hospital/general practitioner visits, need for additional perineal care, dyspareunia, ability to sit comfortably to feed the baby, maternal general health, breastfeeding, wound breakdown, occurrence of anaphylaxis and health-care costs. Results Between March 2016 and June 2018, 3427 women were randomised: 1719 to the antibiotic arm and 1708 to the placebo arm. Seven women withdrew, leaving 1715 women in the antibiotic arm and 1705 in the placebo arm for analysis. Primary outcome data were available for 3225 out of 3420 women (94.3%). Women randomised to the antibiotic arm were significantly less likely to have confirmed or suspected infection within 6 weeks of giving birth (180/1619, 11%) than women randomised to the placebo arm (306/1606, 19%) (relative risk 0.58, 95% confidence interval 0.49 to 0.69). Three serious adverse events were reported: one in the placebo arm and two in the antibiotic arm (one was thought to be causally related to the intervention). Limitations The follow-up rate achieved for most secondary outcomes was 76%. Conclusions This trial has shown clear evidence of benefit of a single intravenous dose of prophylactic co-amoxiclav after operative vaginal birth. These results may lead to reconsideration of official policy/guidance. Further analysis of the mechanism of action of this single dose of antibiotic is needed to investigate whether earlier, pre-delivery or repeated administration could be more effective. Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for pre-delivery administration. Trial registration Current Controlled Trials ISRCTN11166984. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 54. See the National Institute for Health Research Journals Library website for further project information.

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Prophylactic antibiotics for the prevention of infection following operative vaginal delivery (ANODE): study protocol for a randomised controlled trial

Cited by 7 publications

References 16 publications

Operative vaginal delivery and post-partum infection

Operative vaginal delivery and post-partum infection

Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial

Intravenous co-amoxiclav to prevent infection after operative vaginal delivery: the ANODE RCT

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