ORCID Profile
0000-0003-3324-6771
Current Organisation
University of Nottingham
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Publisher: National Institute for Health and Care Research
Date: 2022
DOI: 10.3310/ZZKH4176
Abstract: Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. This took place in one general practice and 19 sexual health centres in the UK. Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms number of recurrences and treatment courses over 6 months microbiological resolution on microscopy of vaginal smears at week 2 time to resolution of symptoms tolerability, adherence and acceptability of the treatment prevalence of concurrent sexually transmitted infections quality of life and cost-effectiveness. Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79% 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204 70%) than with lactic acid gel (97/205 47%) (adjusted risk difference –23.2%, 95% confidence interval –32.3% to –14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71% lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8% taste changes 18% vs. 1% diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal s les would be useful to identify additional factors affecting response to treatment. Current Controlled Trials ISRCTN14161293. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 26, No. 2. See the NIHR Journals Library website for further project information.
Publisher: National Institute for Health and Care Research
Date: 06-2023
DOI: 10.3310/NNZF1037
Abstract: Tubal ectopic pregnancies can cause significant morbidity or even death. Current treatment is with methotrexate or surgery. However, methotrexate treatment can fail in approximately 30% of women. Gefitinib, an epidermal growth factor receptor inhibitor, may improve the effects of methotrexate. We assessed the efficacy of administering oral gefitinib with methotrexate, versus methotrexate alone, to treat a tubal ectopic pregnancy. To test the hypothesis a combination of gefitinib with methotrexate can increase resolution of stable tubal ectopic pregnancy without the need for surgery, compared with methotrexate alone. A randomised, double-blind, placebo-controlled, multicentre, superiority trial. Fifty UK hospitals. A target of 328 women with a stable, tubal ectopic pregnancy. Women were randomised to combination of methotrexate and gefitinib or methotrexate and placebo. All participants received a single intramuscular dose of methotrexate 50 mg/m 2 and were randomised in a 1:1 ratio of oral gefitinib (250 mg daily for 7 days) or placebo. The primary outcome was surgical intervention for resolution of ectopic pregnancy. Secondary outcomes were the need for an additional dose of methotrexate, time to resolution of the ectopic pregnancy, number of treatment-associated hospital visits, safety and tolerability, acceptability of treatment and return to menses. Between 2 November 2016 and 6 October 2021, 328 women were randomly allocated to methotrexate and gefitinib ( n = 165) or methotrexate and placebo ( n = 163). Three women in the placebo group withdrew. Surgical intervention occurred in 30% (50/165) of the gefitinib group and in 29% (47/160) of the placebo group (adjusted risk ratio 1.15, 95% confidence interval 0.85 to 1.58 adjusted risk difference −0.01, 95% confidence interval −0.10 to 0.09 p = 0.37). Without surgical intervention, median time to resolution was 28.0 days in the gefitinib group and 28.0 days in the placebo group (subdistribution hazard ratio 1.03, 95% confidence interval 0.75 to 1.40). The need for additional methotrexate doses, number of additional hospital visits, participant acceptability, time to return of menses and serious adverse events were similar in both groups. Diarrhoea and rash were more common in the gefitinib group. The addition of gefitinib to standard medical management with methotrexate to treat tubal ectopic pregnancy is not clinically effective as it does not reduce subsequent surgical intervention and is associated with higher rates of reported symptoms than placebo. We were unable to investigate how different gefitinib doses or modes of delivery would impact on the results. Questions that remain unaddressed relate to the use of methotrexate and gefitinib combination treatment for other extrauterine and uterine ectopic pregnancy, such as caesarean scar pregnancies, or in the management of choriocarcinoma. This trial is registered as ISRCTN 67795930 and EudraCT 2015-005013-76. This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme and will be published in full in Efficacy and Mechanistic Evaluation Vol. 10, No. 1. The gefitinib and placebo were supplied by Astra Zeneca. See the NIHR Journals Library website for further project information.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jane Daniels.