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Background The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. Funding UK National Institute for Health and Care Research

BackgroundDecline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age.AimTo determine the proportion of participants with a decline in estimated glomerular filtration rate (eGFR), identify determinants of decline, and determine proportions with chronic kidney disease (CKD) remission.Design and settingObservational cohort study in UK primary care.MethodData were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73 m2/year, improvement as eGFR increase >5 ml/min/1.73 m2/year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline.ResultsThere was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement, and 82 of 394 (21%) meeting CKD stage 1–4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure, and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function.ConclusionThis study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care.

Background A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. Methods PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. Findings The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI –0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). Interpretation Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. Funding National Institute of Health Research and United Kingdom Research Innovation.

Background: Colchicine has been proposed as a COVID-19 treatment. Aim: To determine whether colchicine reduces time to recovery and COVID-19 related hospitalisations/deaths among people in the community. Design and setting: Prospective, multicentre, open-label, multi-arm, randomised, controlled adaptive platform trial (PRINCIPLE). Method: Adults aged ≥65, or ≥18 years with comorbidities or shortness of breath, and unwell ≤14 days with suspected COVID-19 in the community were randomised to usual care, usual care plus colchicine (500μg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery, and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. The hypothesis for the time to recovery endpoint is evaluated first, and if superiority is declared on time to recovery, the hypothesis for the second co-primary endpoint of hospitalisation/death is then evaluated. To determine futility, we pre-specified a clinically meaningful benefit in time to first reported recovery as a hazard ratio of 1.2 or larger (equating to approximately 1.5 days benefit in the colchicine arm, assuming 9 days recovery in the usual care arm). Results: The trial opened on April 2, 2020, with randomisation to colchicine from March 04, 2021 until May 26, 2021, after the pre-specified time to recovery futility criterion was met. The primary analysis model included 2755 SARS-CoV-2 positive participants, randomised to colchicine (n=156), usual care (n=1145), and other treatments (n=1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0·919 [95% credible interval 0·72 to 1·16] and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. Results were similar in comparisons with concurrent controls. COVID-19 related hospitalisations/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0·76 [0·28 to 1·89] and an estimated difference of 0.4% [-2.4 to 2.7%]. One serious adverse event occurred in the colchicine group and two in usual care. Conclusions: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.

Background: The safety, effectiveness and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, in patients in the community who are multiply-vaccinated and at increased risk of morbidity and mortality from COVID-19, has not been established. We aimed to determine whether molnupiravir added to usual care reduced hospital admissions/deaths among people at higher risk from COVID-19, and here report our preliminary analyses. Methods: Participants in this UK multicentre, open-label, adaptive, multi-arm, platform, randomised controlled trial were aged ≥50, or ≥18 years with comorbidities, and unwell ≤5 days with confirmed COVID-19 in the community, and were randomised to usual care or usual care plus molnupiravir (800mg twice daily for 5 days). The primary outcome measure was all-cause hospitalisation/death within 28 days, analysed using Bayesian models. The main secondary outcome measure was time to first self-reported recovery. A sub-set of participants in each group were assessed for the virology primary outcome measure of day seven SARS-CoV-2 viral load. Trial registration: ISRCTN30448031 Findings: Between December 8, 2021 and April 27, 2022, 25783 participants were randomised to molnupiravir plus usual care (n=12821) or usual care alone (n=12962). Mean (range) age of participants was 56·6 years (18 to 99), 58·6% were female, and 99% had at least one dose of a SARS-CoV-2 vaccine. The median duration of symptoms prior to randomisation was two days (IQR 1 – 3), the median number of days from symptom onset to starting to take the medication was three days (IQR 3 – 4), 87% (11109/11997) received their medication within five days of symptom onset, and 95·4% (n=11857) of participants randomised to molnupiravir reported taking molnupiravir for five days. Primary outcome measure data were available in 25000 (97%) participants and included in this analysis. 103/12516 (0·8%) hospitalisations/deaths occurred in the molnupiravir group versus 96/12484 (0·8%) in usual care alone with a posterior probability of superiority of 0·34 (adjusted odds ratio 1·061 (95% Bayesian credible interval [BCI]) 0·80 to 1·40). Estimates were similar for all subgroups. The observed median (IQR) time-to-first-recovery from randomisation was 9 (5–23) days in molnupiravir and 15 (7–not reached) days in usual care. There was an estimated benefit of 4·2 (95% BCI: 3·8 – 4·6) days in time-to-first-recovery (TTR) giving a posterior probability of superiority of >0·999 (estimated median TTR 10·3 [10·2 – 10·6] days vs 14·5 [14·2 – 14·9] days respectively; hazard ratio [95% BCI], 1·36 [1·3–1·4] days), which met the pre-specified superiority threshold. On day 7, SARS-CoV-2 virus was below detection levels in 7/34 (21%) of the molnupiravir group, versus 1/39 (3%) in the usual care group (p=0.039), and mean viral load was lower in the molnupiravir group compared with those receiving usual care [(SD) of log10(viral load) 3·82 (1·40) in the molnupiravir group and 4.93 (1·38) in the usual care group, (P Interpretation: In this preliminary analysis, we found that molnupiravir did not reduce already low hospitalisations/deaths among higher risk, vaccinated adults with COVID-19 in the community, but resulted in faster time to recovery, and reduced viral detection and load. Funding: This project is funded by the NIHR (NIHR135366). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

ObjectivesColchicine has been proposed as a COVID-19 treatment, but its effect on time to recovery is unknown. We aimed to determine whether colchicine is effective at reducing time to recovery and COVID-19 related hospitalisations/deaths among people in the community.DesignProspective, multicentre, open-label, multi-arm, adaptive Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses (PRINCIPLE).SettingNational trial run remotely from a central trial site and at multiple primary care centres across the United Kingdom.ParticipantsAdults aged ≥65, or ≥18 years with comorbidities or shortness of breath, and unwell ≤14 days with suspected COVID-19 in the community.InterventionsParticipants were randomised to usual care, usual care plus colchicine (500µg daily for 14 days), or usual care plus other interventions.Main outcome measuresThe co-primary endpoints were time to first self-reported recovery, and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. The hypothesis for the time to recovery endpoint is evaluated first, and if superiority is declared on time to recovery, the hypothesis for the second co-primary endpoint of hospitalisation/death is then evaluated. To determine futility, we pre-specified a clinically meaningful benefit in time to first reported recovery as a hazard ratio of 1.2 or larger (equating to approximately 1.5 days benefit in the colchicine arm, assuming 9 days recovery in the usual care arm).ResultsThe trial opened on April 2, 2020, with randomisation to colchicine starting on March 04, 2021 and stopping on May 26, 2021, because the pre-specified time to recovery futility criterion was met. The primary analysis model included 2755 SARS-CoV-2 positive participants, randomised to colchicine (n=156), usual care (n=1145), and other treatments (n=1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.919 [95% credible interval 0.72 to 1.16] and an estimated increase of 1.14 days [−1.86 to 5.21] in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. Results were similar in comparisons with concurrent controls. COVID-19 related hospitalisations/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 [0.28 to 1.89] and an estimated difference of −0.4% [−2.7% to 2.4]. One serious adverse event occurred in the colchicine group and one in usual care.ConclusionsColchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.Trial registrationISRCTN86534580.

Background Doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes. Methods We did a national, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in older people (PRINCIPLE) across primary care centres in the UK. We included people aged 65 years or older, or 50 years or older with comorbidities (weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or neurological problem, and self-reported obesity or body-mass index of 35 kg/m2 or greater), who had been unwell (for ≤14 days) with suspected COVID-19 or a positive PCR test for SARS-CoV-2 infection in the community. Participants were randomly assigned using response adaptive randomisation to usual care only, usual care plus oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days), or usual care plus other interventions. The interventions reported in this manuscript are usual care plus doxycycline and usual care only; evaluations of other interventions in this platform trial are ongoing. The coprimary endpoints were time to first self-reported recovery, and hospitalisation or death related to COVID-19, both measured over 28 days from randomisation and analysed by intention to treat. This trial is ongoing and is registered with ISRCTN, 86534580. Findings The trial opened on April 2, 2020. Randomisation to doxycycline began on July 24, 2020, and was stopped on Dec 14, 2020, because the prespecified futility criterion was met; 2689 participants were enrolled and randomised between these dates. Of these, 2508 (93·3%) participants contributed follow-up data and were included in the primary analysis: 780 (31·1%) in the usual care plus doxycycline group, 948 in the usual care only group (37·8%), and 780 (31·1%) in the usual care plus other interventions group. Among the 1792 participants randomly assigned to the usual care plus doxycycline and usual care only groups, the mean age was 61·1 years (SD 7·9); 999 (55·7%) participants were female and 790 (44·1%) were male. In the primary analysis model, there was little evidence of difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian Credible Interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, hazard ratio 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI −0·99 to 2·04] and the probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalisation or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group and 43 (4·5%) in the usual care only group (estimated absolute percentage difference −0·5% [95% BCI −2·6 to 1·4]); there were five deaths (0·6%) in the usual care plus doxycycline group and two (0·2%) in the usual care only group. Interpretation In patients with suspected COVID-19 in the community in the UK, who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths related to COVID-19, and should not be used as a routine treatment for COVID-19. Funding UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research.

IntroductionThere is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications.Methods and analysisThe Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50–64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 ‘hot hubs’ and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes.Ethics and disseminationEthical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals.Trial registration numberISRCTN86534580.

Background Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. Aim The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. Methods We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. Key results Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. Conclusion A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.

Objectives To establish the prevalence of multimorbidity in people with chronic kidney disease (CKD) stages 1–5 and transiently impaired renal function and identify factors associated with multimorbidity. Design and setting Prospective cohort study in UK primary care. Participants 861 participants aged 60 and older with decreased renal function of whom, 584 (65.8%) had CKD and 277 (32.2%) did not have CKD. Interventions Participants underwent medical history and clinical assessment, and blood and urine sampling. Primary and secondary outcome measures Multimorbidity was defined as presence of ≥2 chronic conditions including CKD. Prevalence of each condition, co-existing conditions and multimorbidity were described and logistic regression was used to identify predictors of multimorbidity. Results The mean (±SD) age of participants was 74±7 years, 54% were women and 98% were white. After CKD, the next most prevalent condition was hypertension (n = 511, 59.3%), followed by obesity (n = 265, 30.8%) ischemic heart disease (n = 145, 16.8%) and diabetes (n = 133, 15.4%). Having two co-existing conditions was most common (27%), the most common combination of which was hypertension and obesity (29%). One or three conditions was the next most prevalent combination (20% and 21% respectively). The prevalence of multimorbidity was 73.9% (95%CI 70.9–76.8) in all participants and 86.6% (95%CI 83.9–89.3) in those with any-stage CKD. Logistic regression found a significant association between increasing age (OR 1.07, 95%CI 1.04–0.10), increasing BMI (OR 1.15, 95%CI 1.10–1.20) and decreasing eGFR (OR 0.99, 95%CI 0.98–1.00) with multimorbidity. Conclusions This analysis is the first to provide an accurate estimate of the prevalence of multimorbidity in a screened older primary care population living with or at risk of CKD across all stages. Hypertension and obesity were the most common combination of conditions other than CKD that people were living with, suggesting that there may be multiple reasons for closely monitoring health status in individuals with CKD.

IntroductionRecent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multimorbidity. However, there is a lack of evidence to support deprescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up.Methods and analysisThis trial will use a primary care-based, open-label, randomised controlled trial design. A total of 540 participants will be recruited, aged ≥80 years, with systolic blood pressure Ethics and disseminationThe protocol, informed consent form, participant information sheet and all other participant facing material have been approved by the Research Ethics Committee (South Central—Oxford A; ref 16/SC/0628), Medicines and Healthcare products Regulatory Agency (ref 21584/0371/001–0001), host institution(s) and Health Research Authority. All research outputs will be published in peer-reviewed journals and presented at national and international conferences.Trial registration numberEudraCT 2016-004236-38;ISRCTN97503221; Pre-results.

BACKGROUND: Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care.METHODS: This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mm Hg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisation was by a secure web-based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pressure at 12 months from randomisation. Primary analysis was of available cases. The trial is registered with ISRCTN, number ISRCTN 83571366.FINDINGS: 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups compared with usual care (self-monitoring, 137·0 [SD 16·7] mm Hg and telemonitoring, 136·0 [16·1] mm Hg vs usual care, 140·4 [16·5]; adjusted mean differences vs usual care: self-monitoring alone, -3·5 mm Hg [95% CI -5·8 to -1·2]; telemonitoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups.INTERPRETATION: Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individuals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care.FUNDING: National Institute for Health Research via Programme Grant for Applied Health Research (RP-PG-1209-10051), Professorship to RJM (NIHR-RP-R2-12-015), Oxford Collaboration for Leadership in Applied Health Research and Care, and Omron Healthcare UK.

BackgroundChronic kidney disease (CKD) is diagnosed using the estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (ACR). The eGFR is calculated from serum creatinine levels using the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.AimTo compare the performance of one versus two eGFR/ACR measurements, and the impact of equation choice, on CKD diagnosis and classification.Design and settingCohort study in primary care in the Thames Valley region of the UK.MethodData were from 485 participants aged >60 years in the Oxford Renal Cohort Study with at least two eGFR tests. The proportion of study participants diagnosed and classified into different CKD stages using one and two positive tests were compared. Prevalence of CKD diagnosis and classification by CKD stage were compared when eGFR was calculated using MDRD and CKD-EPI equations.ResultsParticipants included in the analysis had a mean age of 72.1 (±6.8) years and 57.0% were female. Use of a single screening test overestimated the proportion of people with CKD by around 25% no matter which equation was used, compared with the use of two tests. The mean eGFR was 1.4 ml/min/1.73 m2 (95% CI = 1.1 to 1.6) higher using the CKD-EPI equation compared with the MDRD equation. More patients were diagnosed with CKD when using the MDRD equation, compared with the CKD-EPI equation, once (64% versus 63%, respectively) and twice (39% versus 38%, respectively), and 16 individuals, all of who had CKD stages 2 or 3A with MDRD, were reclassified as having a normal urinary ACR when using the CKD-EPI equation.ConclusionCurrent guidance to use two eGFR measures to diagnose CKD remains appropriate in an older primary care population to avoid overdiagnosis. A change from MDRD to CKD-EPI equation could result in one in 12 patients with a CKD diagnosis with MDRD no longer having a diagnosis of CKD.

Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared to usual care.

Large, simple, pragmatic, low-risk, maintenance treatment\ud trials may seem straightforward to design, run and\ud analyse. However, if trial case record forms (CRFs) are\ud completed infrequently, the reliability of patient recall\ud over these long time-periods is questionable, especially\ud when recording individual incidences and severity of\ud toxicities of specific interest to the trial. It is essential to\ud know these detailed toxicities as it forms an indication\ud of the reduced level of exposure when comparing treatment\ud duration in a non-inferiority trial. Optimal methods\ud of achieving accurate data are required.

TPS656 Background: PERSEPHONE is a randomised controlled trial comparing six months of trastuzumab to the standard 12 months in patients with HER2 positive early breast cancer. Methods: 4,000 patie...

552 Background: PERSEPHONE is a randomised trial comparing 6month (6m) to 12month (12m) of trastuzumab in patients (pts) with HER2-positive early breast cancer. The trial has recruited 3,166 of 4,0...

TPS660 Background: Persephone is a phase III randomised controlled trial comparing six months of trastuzumab to the standard 12 month duration in patients with HER2 positive early breast cancer in respect of disease free survival, safety and cost-effectiveness. A Persephone sister study, the PHARE trial run by the National Institute for Cancer, successfully closed to recruitment in 2010. A prospective meta-analysis is planned once each trial has reported individually. Methods: A total of 4000 patients will be randomised into each of the two treatment groups. The power calculations assume that the disease-free survival (DFS) of the standard treatment of 12 months trastuzumab will be 80% at 4 years. On this basis, with 5% 1-sided significance and 85% power, a trial randomising 2000 in each arm will have the ability to prove non-inferiority of the experimental arm defining non-inferiority as ‘no worse than 3%’ below the control arm 4 year DFS. Primary outcome is disease-free survival non-inferiority (equivalence) of 6 months trastuzumab compared with 12 months in women with early breast cancer. Secondary outcomes are overall survival non-inferiority (equivalence); expected incremental cost effectiveness; cardiology function and analysis of predictive factors for development of cardiac damage. Two mandatory sub-studies are: Tumour block collection to discover molecular predictors of survival with respect to duration of trastuzumab treatment and blood sample collection, used to discover single nucleotide polymorphisms (SNPs) as genetic/pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. A third optional sub-study is the quality of life questionnaires. Results: Persephone opened to recruitment in October 2007. To date, 1847 patients (46%) of its total have been randomised from 147 UK sites. Recruitment is due to complete by December 2013 and the first planned interim analysis of the primary outcome will be mid-2016. The IDSMC last reviewed the trial in June 2011 and congratulated the Trial Management Group on the conduct of the trial and the quality of the data. No safety concerns were identified, and the IDSMC proposed that the trial continue to planned recruitment.