Corticosteroids injections versus corticosteroids with hyaluronic acid injections in rhizarthrosis: the randomised multicentre RHIZ’ART trial study protocol

IntroductionOsteoarthritis of the trapeziometacarpal joint affects approximately 10%–25% of women, especially those who are postmenopausal. It may result in thumb dysfunction. Among the treatments, intra-articular injections of corticosteroid (CS) and hyaluronic acid (HA) are both effective and recommended. However, clinical trials have shown that HA improves functional capacity, whereas CS only produces a decrease in pain. The synergy of these two drugs has not been evaluated. The primary goal of this study was to determine whether the association between HA and CS produce an additional decrease of more pain during thumb movement at three months postinjection, compared to the level of pain relief from CS alone.Methods and analysisRHIZ’ART is a prospective, multicentre, comparative, randomised, controlled, double-blind trial. Patients referred to the rheumatology department for thumb rhizarthrosis will receive an injection of betamethasone with HA or placebo (serum saline) based on central randomisation and stratification by centre. Injections will be given under ultrasound guidance. The primary outcome will compare the pain Visual Analogue Scale with motion at three months for both groups using a mixed model. The expected decrease in pain intensity in the CS group is 25% and 35% in the CS with HA group. In order to achieve a 80% power for detecting this difference with α set at 5%, 73 patients are needed in each group (146 total). The main secondary outcomes are the Cochin score (hand function) and grip strength. Follow-up visits are at 1, 3, 6 and 12 months.Ethics and disseminationThe study project has been approved by the appropriate ethics committee (CPP île de France III, 2017-002298-20). In agreement with current French regulations, a signed informed written consent will be obtained from each patient. Results of the main trial and of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03431584.

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Nurse-based secondary preventive follow-up by telephone reduced recurrence of cardiovascular events: a randomised controlled trial

Scientific Reports ◽

10.1038/s41598-021-94892-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna-Lotta Irewall ◽

Anders Ulvenstam ◽

Anna Graipe ◽

Joachim Ögren ◽

Thomas Mooe

Keyword(s):

Randomised Controlled Trial ◽

Primary Endpoint ◽

Cardiovascular Events ◽

Controlled Trial ◽

Control Group ◽

Coronary Syndrome ◽

Secondary Endpoints ◽

Randomised Controlled

AbstractEnhanced follow-up is needed to improve the results of secondary preventive care in patients with established cardiovascular disease. We examined the effect of long-term, nurse-based, secondary preventive follow-up by telephone on the recurrence of cardiovascular events. Open, randomised, controlled trial with two parallel groups. Between 1 January 2010 and 31 December 2014, consecutive patients (n = 1890) admitted to hospital due to stroke, transient ischaemic attack (TIA), or acute coronary syndrome (ACS) were included. Participants were randomised (1:1) to nurse-based telephone follow-up (intervention, n = 944) or usual care (control, n = 946) and followed until 31 December 2017. The primary endpoint was a composite of stroke, myocardial infarction, cardiac revascularisation, and cardiovascular death. The individual components of the primary endpoint, TIA, and all-cause mortality were analysed as secondary endpoints. The assessment of outcome events was blinded to study group assignment. After a mean follow-up of 4.5 years, 22.7% (n = 214) of patients in the intervention group and 27.1% (n = 256) in the control group reached the primary composite endpoint (HR 0.81, 95% CI 0.68–0.97; ARR 4.4%, 95% CI 0.5–8.3). Secondary endpoints did not differ significantly between groups. Nurse-based secondary preventive follow-up by telephone reduced the recurrence of cardiovascular events during long-term follow-up.

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Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Cephalalgia ◽

10.1177/0333102421989232 ◽

2021 ◽

Vol 41 (3) ◽

pp. 294-304 ◽

Cited By ~ 2

Author(s):

Messoud Ashina ◽

Uwe Reuter ◽

Timothy Smith ◽

Judith Krikke-Workel ◽

Suzanne R Klise ◽

...

Keyword(s):

Controlled Trial ◽

Study Drug ◽

Statistical Testing ◽

Control Group ◽

Double Blind ◽

Treatment Groups ◽

Primary Endpoints ◽

Registration Number ◽

Secondary Endpoints ◽

Common Teaes

Background We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks. Methods Patients were randomized 1:1:1 to one of three treatment groups – lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity. Results Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg ( p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity. Conclusions These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks. Trial Registration Number: NCT03670810

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Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial

The Lancet Respiratory Medicine ◽

10.1016/s2213-2600(15)00319-7 ◽

2015 ◽

Vol 3 (9) ◽

pp. 702-708 ◽

Cited By ~ 16

Author(s):

Håvard Ove Skjerven ◽

Leif Bjarte Rolfsjord ◽

Teresa Løvold Berents ◽

Hanne Engen ◽

Edin Dizdarevic ◽

...

Keyword(s):

Allergic Diseases ◽

Acute Bronchiolitis ◽

Double Blind ◽

Randomised Controlled

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Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211682 ◽

2017 ◽

Vol 77 (2) ◽

pp. 212-220 ◽

Cited By ~ 111

Author(s):

Dinesh Khanna ◽

Christopher P Denton ◽

Celia J F Lin ◽

Jacob M van Laar ◽

Tracy M Frech ◽

...

Keyword(s):

Systemic Sclerosis ◽

Phase Ii ◽

Controlled Trial ◽

Safety Data ◽

Open Label ◽

Double Blind ◽

Skin Score ◽

Open Label Extension ◽

Registration Number ◽

Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

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Can topical epinephrine application to the papilla prevent pancreatitis after endoscopic retrograde cholangiopancreatography? Results from a double blind, multicentre, placebo controlled, randomised clinical trial

BMJ Open Gastroenterology ◽

10.1136/bmjgast-2020-000562 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000562

Author(s):

Adriana Fabiola Romano-Munive ◽

J Jesus García-Correa ◽

Luis F García-Contreras ◽

José Ramírez-García ◽

Luis Uscanga ◽

...

Keyword(s):

Endoscopic Retrograde Cholangiopancreatography ◽

Controlled Trial ◽

Randomised Clinical Trial ◽

Sterile Water ◽

Endoscopic Retrograde ◽

Double Blind ◽

Registration Number ◽

Baseline Characteristics ◽

Randomised Controlled ◽

Rectal Indomethacin

Background and study aimsPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a complication associated with important morbidity, occasional mortality and high costs. Preventive strategies are suboptimal as PEP continues to affect 4% to 9% of patients. Spraying epinephrine on the papilla may decrease oedema and prevent PEP. This study aimed to compare rectal indomethacin plus epinephrine (EI) versus rectal indomethacin plus sterile water (WI) for the prevention of PEP.Patients and methodsThis multicentre randomised controlled trial included patients aged >18 years with an indication for ERCP and naive major papilla. All patients received 100 mg of rectal indomethacin and 10 mL of sterile water or a 1:10 000 epinephrine dilution. Patients were asked about PEP symptoms via telephone 24 hours and 7 days after the procedure. The trial was stopped half way through after a new publication reported an increased incidence of PEP among patients receiving epinephrine.ResultsOf the 3602 patients deemed eligible, 3054 were excluded after screening. The remaining 548 patients were randomised to EI group (n=275) or WI group (n=273). The EI and WI groups had similar baseline characteristics. Patients in the EI group had a similar incidence of PEP to those in the WI group (3.6% (10/275) vs 5.12% (14/273), p=0.41). Pancreatic duct guidewire insertion was identified as a risk factor for PEP (OR 4.38, 95% CI (1.44 to 13.29), p=0.009).ConclusionSpraying epinephrine on the papilla was no more effective than rectal indomethacin alone for the prevention of PEP.Trial registration numberThis study was registered with ClinicalTrials.gov (NCT02959112).

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Effect of antenatal multiple micronutrient supplementation on anthropometry and blood pressure in mid-childhood in Nepal: follow-up of a double-blind randomised controlled trial

The Lancet Global Health ◽

10.1016/s2214-109x(14)70314-6 ◽

2014 ◽

Vol 2 (11) ◽

pp. e654-e663 ◽

Cited By ~ 28

Author(s):

Delan Devakumar ◽

Shiva Shankar Chaube ◽

Jonathan C K Wells ◽

Naomi M Saville ◽

Jon G Ayres ◽

...

Keyword(s):

Blood Pressure ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Micronutrient Supplementation ◽

Double Blind ◽

Multiple Micronutrient ◽

Randomised Controlled

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Rezafungin versus Caspofungin in a Phase 2, Randomized, Double-Blind Study for the Treatment of Candidemia and Invasive Candidiasis- The STRIVE Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1380 ◽

2020 ◽

Author(s):

George R Thompson ◽

Alex Soriano ◽

Athanasios Skoutelis ◽

Jose A Vazquez ◽

Patrick M Honore ◽

...

Keyword(s):

Invasive Candidiasis ◽

Double Blind Study ◽

Phase 2 ◽

Double Blind ◽

Once Daily ◽

Secondary Endpoints ◽

Intent To Treat ◽

Cure Rates ◽

Treat Population

Abstract Background Rezafungin (RZF) is a novel echinocandin exhibiting distinctive pharmacokinetics/pharmacodynamics. STRIVE was a phase 2, double-blind, randomized trial designed to compare the safety and efficacy of RZF once weekly (QWk) to caspofungin (CAS) once daily for treatment of candidemia and/or invasive candidiasis (IC). Methods Adults with systemic signs and mycological confirmation of candidemia and/or IC were randomized to RZF 400 mg QWk (400 mg), RZF 400 mg on week 1 then 200 mg QWk (400/200 mg), or CAS 70 mg as a loading dose followed by 50 mg daily for ≤ 4 weeks. Efficacy assessments included overall cure (resolution of signs of candidemia/IC + mycological eradication) at day 14 (primary endpoint), investigator-assessed clinical response at day 14, and 30-day all-cause mortality (ACM) (secondary endpoints), and time to negative blood culture. Safety was evaluated by adverse events and ACM through follow-up. Results Of 207 patients enrolled, 183 were in the microbiological intent-to-treat population (~21% IC). Overall cure rates were 60.5% (46/76) for RZF 400 mg, 76.1% (35/46) for RZF 400/200 mg, and 67.2% (41/61) for CAS; investigator-assessed clinical cure rates were 69.7% (53/76), 80.4% (37/46), and 70.5% (43/61), respectively. 30-day ACM was 15.8% for RZF 400 mg, 4.4% for RZF 400/200 mg, and 13.1% for CAS. Candidemia was cleared in 19.5 and 22.8 hours in RZF and CAS patients, respectively. No concerning safety trends were observed; ACM through follow-up was 15.2% (21/138) for RZF and 18.8% (13/69) for CAS. Conclusions RZF was safe and efficacious in the treatment of candidemia and/or IC.

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Effectiveness assessment of riluzole in the prevention of oxaliplatin-induced peripheral neuropathy: RILUZOX-01: protocol of a randomised, parallel, controlled, double-blind and multicentre study by the UNICANCER-AFSOS Supportive Care intergroup

BMJ Open ◽

10.1136/bmjopen-2018-027770 ◽

2019 ◽

Vol 9 (6) ◽

pp. e027770 ◽

Cited By ~ 5

Author(s):

Nicolas Kerckhove ◽

Jérome Busserolles ◽

Trevor Stanbury ◽

Bruno Pereira ◽

Valérie Plence ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Disease Free Survival ◽

Sensory Neuropathy ◽

Repeated Administration ◽

Public Health Issue ◽

Double Blind Study ◽

Double Blind ◽

Related Quality ◽

Registration Number ◽

Randomised Controlled

IntroductionMost patients (>70%) experience acute neuropathic symptoms shortly after oxaliplatin infusions. These symptoms are not always resolved between infusions. Overall, 30%–50% of patients suffer from chronic oxaliplatin-induced peripheral neuropathy (OIPN). This cumulative and dose-dependent sensory neuropathy limits compliance or results in oxaliplatin-based chemotherapies to be substituted with less neurotoxic agents. These treatment changes impair clinical outcomes, and may be associated with comorbidities, such as distress, depression and anxiety. Currently, no drug used to prevent or treat OIPN is sufficiently effective to be used routinely in clinical practice. There is, thus, an unmet therapeutic need to reduce the intensity of and/or prevent OIPN. We hypothesised that riluzole would be an excellent candidate to address this public health issue. Riluzole is approved for treating amyotrophic lateral sclerosis. In animals, there is a beneficial effect on sensorimotor and pain disorders, as well as related comorbidities, after repeated administration of oxaliplatin. In humans, riluzole has shown neuroprotective, anxiolytic and antidepressive effects.Methods and analysisRILUZOX-01 trial was designed as a randomised, controlled, double-blind study to evaluate the efficacy of riluzole to prevent OIPN. Patients with colorectal cancer and initiating adjuvant oxaliplatin-based chemotherapy are eligible. Patients (n=210) will be randomly assigned to either riluzole or placebo, concomitantly with chemotherapy. The primary endpoint is the change in OIPN intensity, assessed by the sensory scale of the QLQ-CIPN20, after six 2-week cycles of chemotherapy. Secondary endpoints include incidence and severity of neuropathy, grade of sensory neuropathy, intensity and features of neuropathic pain, health-related quality of life, disease-free survival, overall survival and safety.Ethics and dessiminationThe study was approved by a French ethics committee (ref:39/18_1, ‘Comité de Protection des Personnes’ Ouest-IV, France) and plans to start enroling patients in September 2019. The trial is registered in EudraCT and clinicaltrials.gov.Trial registration numberN°2017-002320-25;NCT03722680

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Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

BMJ Global Health ◽

10.1136/bmjgh-2020-003897 ◽

2020 ◽

Vol 5 (12) ◽

pp. e003897

Author(s):

Kaitlyn L I Samson ◽

Su Peng Loh ◽

Siew Siew Lee ◽

Dian C Sulistyoningrum ◽

Geok Lin Khor ◽

...

Keyword(s):

Folic Acid ◽

Neural Tube ◽

Controlled Trial ◽

Clinical Trial Registry ◽

Double Blind ◽

Folic Acid Supplements ◽

Registration Number ◽

Menstruating Women ◽

Iron Folic Acid ◽

Randomised Controlled

IntroductionWeekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.MethodsWe conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.ResultsAt 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.ConclusionWeekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed.Trail registration numberThis trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

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