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The Cochrane Database of Systematic... Apr 2021Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014.
OBJECTIVES
To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy.
MAIN RESULTS
In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability.
AUTHORS' CONCLUSIONS
Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.
Topics: Bias; Cesarean Section; Diabetes, Gestational; Female; Humans; Obesity; Overweight; Placebos; Pre-Eclampsia; Pregnancy; Probiotics; Randomized Controlled Trials as Topic
PubMed: 33870484
DOI: 10.1002/14651858.CD009951.pub3 -
Circulation Aug 2021Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease.
METHODS
In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat.
RESULTS
A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78-1.49]; =0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events.
CONCLUSIONS
Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia. Registration: URL: https://www.isrctn.com; Unique identifier ISRCTN16123934.
Topics: Adult; Biomarkers; Comorbidity; Female; Gestational Age; Humans; Incidence; Kaplan-Meier Estimate; Mass Screening; Medication Adherence; Placebos; Pravastatin; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prognosis; Risk Assessment; Risk Factors; Treatment Outcome; Young Adult
PubMed: 34162218
DOI: 10.1161/CIRCULATIONAHA.121.053963 -
The Cochrane Database of Systematic... Aug 2020The symptoms and signs of schizophrenia have been linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The symptoms and signs of schizophrenia have been linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotic drugs are also effective for relapse prevention. This is the updated version of the aforesaid review.
OBJECTIVES
To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (12 November 2008, 10 October 2017, 3 July 2018, 11 September 2019).
SELECTION CRITERIA
We included all randomised trials comparing maintenance treatment with antipsychotic drugs and placebo for people with schizophrenia or schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) or standardised mean differences (SMD), again based on a random-effects model.
MAIN RESULTS
The review currently includes 75 randomised controlled trials (RCTs) involving 9145 participants comparing antipsychotic medication with placebo. The trials were published from 1959 to 2017 and their size ranged between 14 and 420 participants. In many studies the methods of randomisation, allocation and blinding were poorly reported. However, restricting the analysis to studies at low risk of bias gave similar results. Although this and other potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR 0.38, 95% CI 0.32 to 0.45, number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 3; high-certainty evidence). Hospitalisation was also reduced, however, the baseline risk was lower (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR 0.43, 95% CI 0.32 to 0.57, NNTB 8, 95% CI 6 to 14; high-certainty evidence). More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at seven to 12 months: drug 36% versus placebo 62%, 24 RCTs, n = 3951, RR 0.56, 95% CI 0.48 to 0.65, NNTB 4, 95% CI 3 to 5; high-certainty evidence) and due to inefficacy of treatment (at seven to 12 months: drug 18% versus placebo 46%, 24 RCTs, n = 3951, RR 0.37, 95% CI 0.31 to 0.44, NNTB 3, 95% CI 3 to 4). Quality of life might be better in drug-treated participants (7 RCTs, n = 1573 SMD -0.32, 95% CI to -0.57 to -0.07; low-certainty evidence); probably the same for social functioning (15 RCTs, n = 3588, SMD -0.43, 95% CI -0.53 to -0.34; moderate-certainty evidence). Underpowered data revealed no evidence of a difference between groups for the outcome 'Death due to suicide' (drug 0.04% versus placebo 0.1%, 19 RCTs, n = 4634, RR 0.60, 95% CI 0.12 to 2.97,low-certainty evidence) and for the number of participants in employment (at 9 to 15 months, drug 39% versus placebo 34%, 3 RCTs, n = 593, RR 1.08, 95% CI 0.82 to 1.41, low certainty evidence). Antipsychotic drugs (as a group and irrespective of duration) were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI 1.25 to 1.85, number needed to treat for an additional harmful outcome (NNTH) 20, 95% CI 14 to 50), sedation (drug 8% versus placebo 5%, 18 RCTs, n = 4078, RR 1.52, 95% CI 1.24 to 1.86, NNTH 50, 95% CI not significant), and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR 1.69, 95% CI 1.21 to 2.35, NNTH 25, 95% CI 20 to 50).
AUTHORS' CONCLUSIONS
For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs prevents relapse to a much greater extent than placebo for approximately up to two years of follow-up. This effect must be weighed against the adverse effects of antipsychotic drugs. Future studies should better clarify the long-term morbidity and mortality associated with these drugs.
Topics: Antipsychotic Agents; Bias; Dopamine Antagonists; Employment; Hospitalization; Humans; Maintenance Chemotherapy; Patient Dropouts; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Secondary Prevention
PubMed: 32840872
DOI: 10.1002/14651858.CD008016.pub3 -
Gut Microbes 2018Bifidobacterium animalis subsp. lactis HN019 (HN019) ameliorates chronic idiopathic constipation. Our aim was to determine the efficacy and safety of 28-day... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Effects of 28-day Bifidobacterium animalis subsp. lactis HN019 supplementation on colonic transit time and gastrointestinal symptoms in adults with functional constipation: A double-blind, randomized, placebo-controlled, and dose-ranging trial.
Bifidobacterium animalis subsp. lactis HN019 (HN019) ameliorates chronic idiopathic constipation. Our aim was to determine the efficacy and safety of 28-day supplementation with 1 × 10 or 1 × 10 CFU of HN019/day for constipation. A total of 228 adults who were diagnosed with functional constipation according to the Rome III criteria were randomized in a double-blind and placebo-controlled trial. Colonic transit time (CTT), the primary outcome, and secondary outcomes that were measured using inventories-patient assessment of constipation symptoms (PAC-SYM) and quality of life (PAC-QoL), bowel function index (BFI), bowel movement frequency (BMF), stool consistency, degree of straining, bowel emptying, bloating, and pain severity-were assessed. Ancillary parameters and harms were also evaluated. There were no statistically significant differences in the primary or secondary outcomes between interventions. A post hoc analysis of 65 participants with fewer than 3 bowel movements per week (BMF ≤ 3/week) showed a physiologically relevant increase in weekly BMF in the high- (+2.0) and low-dose (+1.7) HN019 groups-by RMANOVA, the HN019 groups with BMF ≤ 3/week, pooled together, had a higher BMF versus placebo (P value = 0.01). Thus, improving low stool frequency could be a target of future interventions with HN019. High-dose HN019 also decreased the degree of straining at Day 28 versus placebo in those with BMF ≤ 3/week (P value = 0.02). Three unlikely related AEs-2 with low-dose HN019 and 1 with placebo-were followed until full recovery. In conclusion, although there were no differences in the primary analysis, HN019 is well tolerated and improves BMF in adults with low stool frequency.
Topics: Adolescent; Adult; Aged; Bifidobacterium animalis; Constipation; Double-Blind Method; Female; Gastrointestinal Transit; Humans; Male; Middle Aged; Placebos; Probiotics; Quality of Life; Treatment Outcome; Young Adult
PubMed: 29227175
DOI: 10.1080/19490976.2017.1412908 -
The Journal of Clinical Endocrinology... Mar 2020The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk... (Comparative Study)
Comparative Study Randomized Controlled Trial
CONTEXT
The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed.
OBJECTIVE
The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend.
DESIGN
In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend.
RESULTS
The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different.
CONCLUSION
Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.
Topics: Aged; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Radiography; Risk Factors; Spinal Fractures; Treatment Outcome
PubMed: 31674644
DOI: 10.1210/clinem/dgz162 -
American Heart Journal Jan 2021Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from...
Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.
Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.
Topics: Aged; Humans; Brain Ischemia; Cholesterol; Coronary Artery Disease; Diabetes Mellitus; Double-Blind Method; Drug Administration Schedule; Hospitalization; Ischemia; Lipoproteins, HDL; Liver; Myocardial Infarction; Myocardial Ischemia; Peripheral Vascular Diseases; Placebos; Plaque, Atherosclerotic; Stroke; Time Factors; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 33065120
DOI: 10.1016/j.ahj.2020.10.052 -
International Review of Neurobiology 2020Placebo effects influence symptom perceptions and treatment outcomes. Placebo effects can be explored in laboratory settings controlling for natural history and... (Review)
Review
Placebo effects influence symptom perceptions and treatment outcomes. Placebo effects can be explored in laboratory settings controlling for natural history and expectations. Such a mechanistic approach to neurological disorders has been implemented in the domain of chronic clinical pain and other neurological disorders. This article therefore focuses on definitions and historical notes related to placebo effects and mechanisms of placebo effects in chronic pain. Knowledge on mechanisms of placebo effects could inform current clinical practice for the treatment of neurological disorders by focusing on patients (and providers) expectations for outcome optimization.
Topics: Analgesia; Anticipation, Psychological; Brain; Chronic Pain; Conditioning, Psychological; Humans; Nervous System Diseases; Placebo Effect; Placebos
PubMed: 32563287
DOI: 10.1016/bs.irn.2020.04.001 -
Journal of Dermatological Science May 2019Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in...
Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2).
BACKGROUND
Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD).
OBJECTIVES
To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety.
METHODS
A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo.
RESULTS
Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0-1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75-<90%/≥50-<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1-3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo.
CONCLUSIONS
Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
Topics: Adult; Antibodies, Monoclonal, Humanized; Anxiety; Clinical Trials, Phase III as Topic; Conjunctivitis; Depression; Dermatitis, Atopic; Female; Humans; Injection Site Reaction; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Measurement; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 31109652
DOI: 10.1016/j.jdermsci.2019.02.002 -
Revue de L'infirmiere May 2019A placebo is used to fight pain, insomnia or anxiety. The placebo effect is said to be this one produced by this 'fake' medication. However, could it not chiefly be the...
A placebo is used to fight pain, insomnia or anxiety. The placebo effect is said to be this one produced by this 'fake' medication. However, could it not chiefly be the effect produced by the trust relationship established between a patient and a caregiver at a given moment? This article reflects on the results of a survey carried out in the hospital sector.
Topics: Anxiety; Health Care Surveys; Humans; Pain; Physician-Patient Relations; Placebo Effect; Placebos; Sleep Initiation and Maintenance Disorders; Trust
PubMed: 31208568
DOI: 10.1016/j.revinf.2019.03.034 -
Future Oncology (London, England) Jan 2020Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant...
Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT03553836.
Topics: Adolescent; Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Chemotherapy, Adjuvant; Child; Clinical Trials, Phase III as Topic; Cross-Over Studies; Dermatologic Surgical Procedures; Disease-Free Survival; Female; Humans; Male; Melanoma; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Neoplasm Staging; Placebos; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic; Skin Neoplasms; Young Adult
PubMed: 31870188
DOI: 10.2217/fon-2019-0666