scholarly journals Cadence discovery: study protocol for a dose-finding and mechanism of action clinical trial of sodium benzoate in people with treatment-refractory schizophrenia

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrea Baker ◽  
Lachlan Clarke ◽  
Peter Donovan ◽  
Jacobus P. J. Ungerer ◽  
Gunter Hartel ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Sodium Benzoate ◽  
Outcome Measurement ◽  
High Sensitivity ◽  
Premature Mortality ◽  
Trial Registration ◽  
Dose Finding ◽  
Secondary Outcome ◽  
Plasma Sodium ◽  
Treatment Refractory

Abstract Background Schizophrenia is a persistent psychotic disorder often accompanied by severe disability and premature mortality. New pharmacological treatments are urgently needed. Sodium benzoate, a common food preservative holds potential to be an effective, accessible treatment for schizophrenia, though the optimal dosing and mechanism of action of the compound requires further investigation. Methods Individuals with persistent treatment-refractory schizophrenia (n=52) will be recruited. Patients will be randomised in a 1:1:1:1 ratio to receive treatment of one of three active doses (1000, 2000 or 4000 mg daily) of sodium benzoate or placebo for 6 weeks duration. The primary outcome measurement is change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measurements are PANSS subscales, Global Assessment of Function (GAF), Clinical Global Impression (CGI) and Patient Global Impression (PGI-I). Change in concentrations of peripheral amino acids (D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate), plasma sodium benzoate, plasma catalase, 3-nitrotyrosine, malondialdehyde and high-sensitivity C-reactive protein (hs-CRP) will be determined as tertiary measures. Discussion This trial seeks to build upon previous research indicating potential efficacy of sodium benzoate for reduction of symptoms in individuals with treatment-refractory schizophrenia. The trial aims to improve the understanding of the mechanism of action of the compound. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000327886. Registered on 23 March 2021.

scholarly journals Fall incidents in nursing home residents: development of a predictive clinical rule (FINDER)

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e042941
Author(s):  
Vanja Milosevic ◽  
Aimee Linkens ◽  
Bjorn Winkens ◽  
Kim P G M Hurkens ◽  
Dennis Wong ◽  
...  
Keyword(s):  
Nursing Home ◽  
Fall Risk ◽  
Nursing Home Residents ◽  
High Sensitivity ◽  
Secondary Outcome ◽  
Operating Characteristics ◽  
Retrospective Case ◽  
Data Set ◽  
Fall Incident ◽  
Clinical Rule

ObjectivesTo develop (part I) and validate (part II) an electronic fall risk clinical rule (CR) to identify nursing home residents (NH-residents) at risk for a fall incident.DesignObservational, retrospective case–control study.SettingNursing homes.ParticipantsA total of 1668 (824 in part I, 844 in part II) NH-residents from the Netherlands were included. Data of participants from part I were excluded in part II.Primary and secondary outcome measuresDevelopment and validation of a fall risk CR in NH-residents. Logistic regression analysis was conducted to identify the fall risk-variables in part I. With these, three CRs were developed (ie, at the day of the fall incident and 3 days and 5 days prior to the fall incident). The overall prediction quality of the CRs were assessed using the area under the receiver operating characteristics (AUROC), and a cut-off value was determined for the predicted risk ensuring a sensitivity ≥0.85. Finally, one CR was chosen and validated in part II using a new retrospective data set.ResultsEleven fall risk-variables were identified in part I. The AUROCs of the three CRs form part I were similar: the AUROC for models I, II and III were 0.714 (95% CI: 0.679 to 0.748), 0.715 (95% CI: 0.680 to 0.750) and 0.709 (95% CI: 0.674 to 0.744), respectively. Model III (ie, 5 days prior to the fall incident) was chosen for validation in part II. The validated AUROC of the CR, obtained in part II, was 0.603 (95% CI: 0.565 to 0.641) with a sensitivity of 83.41% (95% CI: 79.44% to 86.76%) and a specificity of 27.25% (95% CI 23.11% to 31.81%).ConclusionMedication data and resident characteristics alone are not sufficient enough to develop a successful CR with a high sensitivity and specificity to predict fall risk in NH-residents.Trial registration numberNot available.

scholarly journals Occupational therapy and psychosis: POINTER feasibility study for a pragmatic clinical trial

2021 ◽  
pp. 030802262110002
Author(s):  
Joanne Inman ◽  
Katrina Bannigan ◽  
Jacqueline Akhurst
Keyword(s):  
Clinical Trial ◽  
Occupational Therapy ◽  
Everyday Life ◽  
Short Form ◽  
Outcome Measurement ◽  
Performance Measure ◽  
Drop Out ◽  
Secondary Outcome ◽  
Occupational Performance ◽  
Pragmatic Clinical Trial

Introduction The dearth of clinical trials of individualised occupational therapy with people with a diagnosis of psychosis limits the evidence base globally for occupational therapy practice. This study evaluated the feasibility of conducting a pragmatic clinical trial. Method Mixed methods design using a pragmatic perspective; two-centre, one-group pretest-posttest study, at six months. POINTER Occupational Intervention Specification captured routine individualised occupational therapy. Process evaluation included recruitment, retention, intervention delivery, fidelity, adherence and outcome measurement. The primary outcome was participation in activities of everyday life, measured by Time Use Survey, Participation Scale and Utrecht Scale for Evaluation of Rehabilitation-Participation. The Canadian Occupational Performance Measure measured self-reported experience of and satisfaction with occupational performance. The Short Form-36v2 Health Survey measured health-related quality of life, a secondary outcome. Participants’ experiences were explored using a questionnaire. Intervention providers’ perspectives were investigated via the POINTER occupational intervention log and focus groups. Results Recruitment was (20/36) and drop-out 20% (4/20). Fidelity was 77%, and adherence was good; POINTER had validity and utility. Outcome measurement was acceptable to participants, indicating increased participation in activities of everyday life. Conclusion A larger clinical trial is merited; recruitment processes need further exploration, and outcome measurement needs refining.

scholarly journals Effect of Vitamin D Supplementation on Falls, Physical Function, and Activity: Results From the STURDY Trial

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 758-759
Author(s):  
Jennifer Schrack ◽  
Lawrence Appel ◽  
Lewis Lipsitz
Keyword(s):  
Vitamin D ◽  
Fall Prevention ◽  
Gait Speed ◽  
Vitamin D Supplementation ◽  
Dose Finding ◽  
Secondary Outcome ◽  
Skeletal Muscle Function ◽  
Risk Of Falls ◽  
Objectively Measured ◽  
Minute Walk

Abstract Each year, 2.8 million older adults are treated for falls, with over 800,000 hospitalized. Evidence suggests vitamin D supplementation might reduce the risk of falls, potentially through improvements in skeletal muscle function; however, results are inconsistent. In 2013 the NIA issued a request for applications to assess the efficacy and dose-response of vitamin D supplementation for fall prevention across a range of doses and serum 25(OH)D concentrations, resulting in the funding of STURDY (Study To Understand Fall Reduction and Vitamin D in You). STURDY was a seamless dose-finding and confirmatory, double-masked, response adaptive Bayesian randomized trial designed to find the best dose of vitamin D supplementation for fall prevention. Participants (n=688, ≥70 years with serum 25(OH)D of 10-29 ng/mL) were randomized to 200 (control), 1000 , 2000, or 4000 IU/day of vitamin D3.The first participant was randomized on 10/30/2015 and data collection ended on 5/31/2019. The primary outcome was time to first fall or death, and the secondary outcome was gait speed. Dr. Appel will present the main findings of the effect of vitamin D supplementation on time to first fall. Dr. Wanigatunga will present a more detailed analysis of the effect of vitamin D supplementation on fall characteristics, including indoor vs. outdoor falls, consequential falls, and repeat fall risk. Dr. Guralnik will present the effect of vitamin D supplementation on physical functioning, including gait speed, SPPB, 6-minute walk, and TUG performance. Dr. Schrack will present the effect of vitamin D supplementation on objectively measured physical activity.

scholarly journals Bacteriophage-derived CHAP domain protein, P128, kills Staphylococcus cells by cleaving interpeptide cross-bridge of peptidoglycan

Microbiology ◽  
2014 ◽  
Vol 160 (10) ◽  
pp. 2157-2169 ◽  
Author(s):  
Sudarson Sundarrajan ◽  
Junjappa Raghupatil ◽  
Aradhana Vipra ◽  
Nagalakshmi Narasimhaswamy ◽  
Sanjeev Saravanan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Catalytic Domain ◽  
Antibiotic Sensitivity ◽  
High Sensitivity ◽  
Common Mechanism ◽  
Cross Bridge ◽  
Sensitivity Pattern

P128 is an anti-staphylococcal protein consisting of the Staphylococcus aureus phage-K-derived tail-associated muralytic enzyme (TAME) catalytic domain (Lys16) fused with the cell-wall-binding SH3b domain of lysostaphin. In order to understand the mechanism of action and emergence of resistance to P128, we isolated mutants of Staphylococcus spp., including meticillin-resistant Staphylococcus aureus (MRSA), resistant to P128. In addition to P128, the mutants also showed resistance to Lys16, the catalytic domain of P128. The mutants showed loss of fitness as shown by reduced rate of growth in vitro. One of the mutants tested was found to show reduced virulence in animal models of S. aureus septicaemia suggesting loss of fitness in vivo as well. Analysis of the antibiotic sensitivity pattern showed that the mutants derived from MRSA strains had become sensitive to meticillin and other β-lactams. Interestingly, the mutant cells were resistant to the lytic action of phage K, although the phage was able to adsorb to these cells. Sequencing of the femA gene of three P128-resistant mutants showed either a truncation or deletion in femA, suggesting that improper cross-bridge formation in S. aureus could be causing resistance to P128. Using glutathione S-transferase (GST) fusion peptides as substrates it was found that both P128 and Lys16 were capable of cleaving a pentaglycine sequence, suggesting that P128 might be killing S. aureus by cleaving the pentaglycine cross-bridge of peptidoglycan. Moreover, peptides corresponding to the reported cross-bridge of Staphylococcus haemolyticus (GGSGG, AGSGG), which were not cleaved by lysostaphin, were cleaved efficiently by P128. This was also reflected in high sensitivity of S. haemolyticus to P128. This showed that in spite of sharing a common mechanism of action with lysostaphin, P128 has unique properties, which allow it to act on certain lysostaphin-resistant Staphylococcus strains.

scholarly journals Group antenatal care (Pregnancy Circles) for diverse and disadvantaged women: study protocol for a randomised controlled trial with integral process and economic evaluations

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Meg Wiggins ◽  
Mary Sawtell ◽  
Octavia Wiseman ◽  
Christine McCourt ◽  
Sandra Eldridge ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Randomised Controlled Trial ◽  
Antenatal Care ◽  
Standard Care ◽  
Controlled Trial ◽  
Trial Registration ◽  
Secondary Outcome ◽  
The World ◽  
Randomised Controlled

Abstract Background Group antenatal care has been successfully implemented around the world with suggestions of improved outcomes, including for disadvantaged groups, but it has not been formally tested in the UK in the context of the NHS. To address this the REACH Pregnancy Circles intervention was developed and a randomised controlled trial (RCT), based on a pilot study, is in progress. Methods The RCT is a pragmatic, two-arm, individually randomised, parallel group RCT designed to test clinical and cost-effectiveness of REACH Pregnancy Circles compared with standard care. Recruitment will be through NHS services. The sample size is 1732 (866 randomised to the intervention and 866 to standard care). The primary outcome measure is a ‘healthy baby’ composite measured at 1 month postnatal using routine maternity data. Secondary outcome measures will be assessed using participant questionnaires completed at recruitment (baseline), 35 weeks gestation (follow-up 1) and 3 months postnatal (follow-up 2). An integrated process evaluation, to include exploration of fidelity, will be conducted using mixed methods. Analyses will be on an intention to treat as allocated basis. The primary analysis will compare the number of babies born “healthy” in the control and intervention arms and provide an odds ratio. A cost-effectiveness analysis will compare the incremental cost per Quality Adjusted Life Years and per additional ‘healthy and positive birth’ of the intervention with standard care. Qualitative data will be analysed thematically. Discussion This multi-site randomised trial in England is planned to be the largest trial of group antenatal care in the world to date; as well as the first rigorous test within the NHS of this maternity service change. It has a recruitment focus on ethnically, culturally and linguistically diverse and disadvantaged participants, including non-English speakers. Trial registration Trial registration; ISRCTN, ISRCTN91977441. Registered 11 February 2019 - retrospectively registered. The current protocol is Version 4; 28/01/2020.

scholarly journals A feasibility randomised controlled trial of short-term fasting prior to CAPOX chemotherapy for stage 2/3 colorectal cancer: SWiFT protocol

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Ellie Shingler ◽  
Claire Perks ◽  
Georgia Herbert ◽  
Andy Ness ◽  
Charlotte Atkinson
Keyword(s):  
Colorectal Cancer ◽  
Randomised Controlled Trial ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Trial Registration ◽  
Secondary Outcome ◽  
Dietary Advice ◽  
Short Term ◽  
Feasibility Randomised Controlled Trial ◽  
Randomised Controlled

Abstract Background Capecitabine and oxaliplatin (CAPOX) chemotherapy is a standard treatment for stage 2/3 colorectal cancer. Treatment is associated with dose-limiting toxicities such as neutropenia, vomiting, diarrhoea, and stomatitis. Short-term fasting prior to chemotherapy may help protect normal cells from the toxic effects of chemotherapy by allowing them to conserve energy for maintenance and repair. However, there is a lack of evidence to support the efficacy of short-term fasting in protecting against chemotherapy-related toxicities in humans, and it is not known whether people due to undergo chemotherapy will be willing and able to follow a short-term fast. Preliminary data confirming this is feasible are required before adequately powered trials can be designed and conducted. Methods The short-term, water only, fasting trial (SWiFT) is a two-armed feasibility randomised controlled trial, aiming to recruit 30 people scheduled to begin routine treatment with CAPOX chemotherapy for stage 2/3 colorectal cancer. Participants will be randomly allocated, in a 1:1 ratio, to either a 36-h fast or standard dietary advice prior to chemotherapy administration for the first 3 cycles of chemotherapy. The primary outcome measures will assess the feasibility of the trial and include: adherence to intervention, recruitment, retention, and data completion rates as well as the acceptability of the intervention which will be qualitatively assessed. The secondary outcome measures aim to provide further information on possible outcomes of interest for a definitive trial and include side effects of chemotherapy, quality of life, markers of cellular metabolism and inflammation, appetite, and sarcopenia. Discussion It is not known whether it is possible to recruit to a trial of short-term fasting in this population, or whether participants would be able to adhere to the intervention. Therefore, we aim to test the feasibility of a pre-chemotherapy, 36-h, water-only fast in people receiving CAPOX chemotherapy for stage 2/3 colorectal cancer. Trial registration This trial has been registered with the ISRCTN Registry. Trial registration no: ISRCTN17994717. Date of registration: 23 October 2018. URL: http://www.isrctn.com/ISRCTN17994717

scholarly journals Measuring the effects of a personalized music intervention on agitated behaviors among nursing home residents with dementia: design features for cluster-randomized adaptive trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ellen M. McCreedy ◽  
Roee Gutman ◽  
Rosa Baier ◽  
James L. Rudolph ◽  
Kali S. Thomas ◽  
...  
Keyword(s):  
Nursing Home ◽  
Real World ◽  
Implementation Strategies ◽  
Trial Registration ◽  
World Health ◽  
Secondary Outcome ◽  
Link Type ◽  
Cluster Randomized ◽  
The Impact ◽  
Adaptive Trial

Abstract Background Agitated and aggressive behaviors (behaviors) are common in nursing home (NH) residents with dementia. Medications commonly used to manage behaviors have dangerous side effects. NHs are adopting non-pharmacological interventions to manage behaviors, despite a lack of effectiveness evidence and an understanding of optimal implementation strategies. We are conducting an adaptive trial to evaluate the effects of personalized music on behaviors. Adaptive trials may increase efficiency and reduce costs associated with traditional RCTs by learning and making modifications to the trial while it is ongoing. Methods We are conducting two consecutive parallel cluster-randomized trials with 54 NHs in each trial (27 treatment, 27 control). Participating NHs were recruited from 4 corporations which differ in size, ownership structure, geography, and residents’ racial composition. After randomization, there were no significant differences between the NHs randomized to each trial with respect to baseline behaviors, number of eligible residents, degree of cognitive impairment, or antipsychotic use. Agitated behavior frequency is assessed via staff interviews (primary outcome), required nursing staff conducted resident assessments (secondary outcome), and direct observations of residents (secondary outcome). Between the two parallel trials, the adaptive design will be used to test alternative implementation strategies, increasingly enroll residents who are likely to benefit from the intervention, and seamlessly conduct a stage III/IV trial. Discussion This adaptive trial allows investigators to estimate the impact of a popular non-pharmaceutical intervention (personalized music) on residents’ behaviors, under pragmatic, real-world conditions testing two implementation strategies. This design has the potential to reduce the research timeline by improving the likelihood of powered results, increasingly enrolling residents most likely to benefit from intervention, sequentially assessing the effectiveness of implementation strategies in the same trial, and creating a statistical model to reduce the future need for onsite data collection. The design may also increase research equity by enrolling and tailoring the intervention to populations otherwise excluded from research. Our design will inform pragmatic testing of other interventions with limited efficacy evidence but widespread stakeholder adoption because of the real-world need for non-pharmaceutical approaches. {2a} Trial registration ClinicalTrials.govNCT03821844. Registered on January 30, 2019. This trial registration meets the World Health Organization (WHO) minimum standard.

scholarly journals SWAT 76 evaluation: randomised evaluation of sending pre-notification cards to trial participants before a face-to-face primary outcome measurement to increase attendance

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 84
Author(s):  
Shaun Treweek ◽  
Stephanie Gallant ◽  
Annie S. Anderson
Keyword(s):  
Direct Cost ◽  
Primary Outcome ◽  
Outcome Measurement ◽  
Behavioural Change ◽  
Risk Difference ◽  
Secondary Outcome ◽  
Face To Face ◽  
Intention To Treat ◽  
The Uk ◽  
Trial Participants

Background: Retention is considered the second highest trial methods priority in the UK after recruitment.  Methods: This Study Within A Trial (SWAT) evaluated whether sending a pre-notification card around one month before a face-to-face primary outcome measurement visit compared to not sending the card increased trial retention. The SWAT was a two-arm, parallel randomised (1:1 allocation ratio), stratified by centre, study. It was embedded within the ActWELL host trial, which evaluated whether women receiving lifestyle change counselling from volunteer coaches improved outcomes including weight and physical activity. The text on the card was not developed using formal behavioural change theory but did target factors thought to influence attendance. The SWAT primary outcome was the difference in the proportion of participants attending the host trial primary outcome measurement visit. The secondary outcome was the direct cost of sending cards. Host trial participants and research staff at the primary outcome visit were blind to the SWAT. Analysis was intention-to-treat. GRADE was used the assess the certainty of evidence. Results: 558 host trial participants took part in the SWAT and were included in the analysis. Sending a pre-notification card may result in a slight increase in attendance at a face-to-face primary outcome measurement visit: risk difference = 3.3% (95% confidence interval = -3.0% to 9.6%). This is GRADE low certainty evidence. A recording error meant it was unclear whether 17 participants allocated to the card were actually sent one but a sensitivity analysis did not change the overall result or conclusion. The direct cost of producing and sending the cards was £192 GBP (€213 EUR; $260 USD).  Discussion: Trialists could consider using pre-notification as they may gain a slight increase in retention to face-to-face trial measurement visits but further evaluations are needed.

scholarly journals Diagnosing Fetal Skeletal Dysplasia Using Three-Dimensional Computed Tomography: A Study Protocol for an Interventional Study

2020 ◽  
Vol 1 (7) ◽  
pp. 292-296
Author(s):  
Miyoko Waratani ◽  
Fumitake Ito ◽  
Yukiko Tanaka ◽  
Mabuchi Aki ◽  
Taisuke Mori ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Prenatal Diagnosis ◽  
Diagnostic Accuracy ◽  
Radiation Exposure ◽  
Skeletal Dysplasia ◽  
Three Dimensional ◽  
Trial Registration ◽  
Secondary Outcome ◽  
Fetal Imaging ◽  
Skeletal Dysplasias

Background: Fetal skeletal dysplasias are a group of skeletal dysplasias occurring during the fetal stage. As the use of fetal ultrasonography has become widespread, the rate of prenatal diagnosis of skeletal dysplasias has increased. However, many fetal skeletal dysplasia phenotypes have indistinct definitions, making definitive prenatal diagnosis difficult. Fetal imaging methods that are the basis of diagnosing fetal skeletal dysplasias include ultrasonography and three-dimensional computed tomography. The use of three-dimensional computed tomography requires specific imaging techniques and cannot easily be performed at all facilities. In the present study, we propose to conduct a survey for the preparation of a protocol with a low risk, and a high diagnostic accuracy. Methods: In total, 50 pregnant women who undergo three-dimensional computed tomography for the diagnosis of fetal skeletal dysplasias will be included. The primary outcome is prenatal diagnostic accuracy for fetuses with skeletal dysplasias. The secondary outcome is the safety from radiation exposure. Results and conclusion: Three-dimensional computed tomography should be considered for the prenatal diagnosis of fetal skeletal dysplasias, as it is important to judge whether the prognosis is favorable or lethal. When considering the risk of radiation exposure, high quality images that are adequate for a diagnosis have been obtained using low-dose three-dimensional computed tomography scans. This approach reduces the level of radiation to which the pregnant woman and fetus are exposed. Trial registration: University hospital Medical Information Network (UMIN) Center: Trial registration number is UMIN000034744. Data of registration is October 01, 2018. (URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039610).

scholarly journals Safety and efficacy of regorafenib in patients with treatment-refractory metastatic colorectal cancer in Turkey: the single-arm, open-label REGARD study

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e027665
Author(s):  
Faysal Dane ◽  
Kirhan Ozgurdal ◽  
Şuayib Yalçın ◽  
Mustafa Benekli ◽  
Nuri Faruk Aykan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Group Performance ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Open Label ◽  
Safety And Efficacy ◽  
Treatment Refractory ◽  
Grade 3

ObjectivesRegorafenib improved overall survival in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies in two randomised, phase III trials, but has not been evaluated in Turkey. REGARD evaluated the safety and efficacy of regorafenib in Turkish patients with treatment-refractory mCRC.DesignOpen-label, single-arm, phase IIIb study conducted between July 2013 and April 2015.Setting11 tertiary centres in Turkey.ParticipantsEligible patients were adults with mCRC who had disease progression within 3 months after receiving their last dose of approved standard therapies and who had an Eastern Cooperative Oncology Group performance status ≤1. Patients were excluded if they had previously received regorafenib. Of 139 patients screened, 100 were treated and completed the study, and all 100 were analysed. Fifty-eight per cent were male.InterventionsPatients received oral regorafenib, 160 mg once daily, for the first 3 weeks of each 4-week cycle until disease progression, death or unacceptable toxicity.Primary and secondary outcome measuresThe primary endpoint was safety, assessed by incidence of treatment-emergent adverse events (TEAEs). Progression-free survival (PFS) per investigator was the primary efficacy endpoint. There were no secondary endpoints.ResultsThe median treatment duration was 2.5 months (range 0.1 to 20.6). Ninety-six per cent of patients had at least one TEAE and 77% had a grade ≥3 TEAE. The most common grade ≥3 regorafenib-related TEAEs were hypophosphataemia (11%), fatigue (8%), hyperbilirubinaemia (6%), hand–foot skin reaction (5%), hypertension (5%), anorexia (5%) and increased alanine aminotransferase (5%). TEAEs led to dose reduction in 30% of patients. Regorafenib-related TEAEs led to treatment discontinuation in 17% of patients. Median PFS was 3.1 months (95% CI 2.9 to 3.8).ConclusionThe regorafenib safety profile and PFS in REGARD were consistent with the results of previous trials of regorafenib in mCRC. Regorafenib is an option for patients in Turkey with treatment-refractory mCRC.Trial registration numberNCT01853319, ClinicalTrials.gov.

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