A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol

IntroductionRecent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In CT-confirmed uncomplicated acute diverticulitis (left-sided appendicitis), studies have shown no benefit from antibiotics compared with symptomatic treatment, but this shift from antibiotics to symptomatic treatment has not yet been widely implemented in clinical practice. Recently, symptomatic treatment of uncomplicated acute appendicitis has been demonstrated in a Korean open-label study. However, a double-blinded placebo-controlled study to illustrate the role of antibiotics and spontaneous resolution of uncomplicated acute appendicitis is still lacking.Methods and analysisThe APPAC III (APPendicitis ACuta III) trial is a multicentre, double-blind, placebo-controlled, superiority randomised study comparing antibiotic therapy with placebo in the treatment CT scan-confirmed uncomplicated acute appendicitis aiming to evaluate the role of antibiotics in the resolution of uncomplicated acute appendicitis. Adult patients (18–60 years) with CT scan-confirmed uncomplicated acute appendicitis (the absence of appendicolith, abscess, perforation and tumour) will be enrolled in five Finnish university hospitals.Primary endpoint is success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without surgical intervention within 10 days after initiating randomised treatment (treatment efficacy). Secondary endpoints include postintervention complications, recurrent symptoms after treatment up to 1 year, late recurrence of acute appendicitis after 1 year, duration of hospital stay, sick leave, treatment costs and quality of life. A decrease of 15 percentage points in success rate is considered clinically important difference. The superiority of antibiotic treatment compared with placebo will be analysed using Fisher’s one-sided test and CI will be calculated for proportion difference.Ethics and disseminationThis protocol has been approved by the Ethics Committee of Turku University Hospital and the Finnish Medicines Agency (FIMEA). The findings will be disseminated in peer-reviewed academic journals.Trial registration numberNCT03234296; Pre-results.

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Prospective multicentre cohort trial on acute appendicitis and microbiota, aetiology and effects of antimicrobial treatment: study protocol for the MAPPAC (Microbiology APPendicitis ACuta) trial

BMJ Open ◽

10.1136/bmjopen-2019-031137 ◽

2019 ◽

Vol 9 (9) ◽

pp. e031137 ◽

Cited By ~ 2

Author(s):

Sanja Vanhatalo ◽

Eveliina Munukka ◽

Suvi Sippola ◽

Sirpa Jalkanen ◽

Juha Grönroos ◽

...

Keyword(s):

Acute Appendicitis ◽

Clinical Data ◽

Antimicrobial Treatment ◽

Complicated Appendicitis ◽

University Hospital ◽

Serum Samples ◽

Double Blind ◽

Hospital District ◽

Link Type ◽

Uncomplicated Acute Appendicitis

IntroductionBased on the epidemiological and clinical data, acute appendicitis can present either as uncomplicated or complicated. The aetiology of these different appendicitis forms remains unknown. Antibiotic therapy has been shown to be safe, efficient and cost-effective for CT-confirmed uncomplicated acute appendicitis. Despite appendicitis being one of the most common surgical emergencies, there are very few reports on appendicitis aetiology and pathophysiology focusing on the differences between uncomplicated and complicated appendicitis. Microbiology APPendicitis ACuta (MAPPAC) trial aims to evaluate these microbiological and immunological aspects including immune response in the aetiology of these different forms also assessing both antibiotics non-responders and appendicitis recurrence. In addition, MAPPAC aims to determine antibiotic and placebo effects on gut microbiota composition and antimicrobial resistance.Methods and analysisMAPPAC is a prospective clinical trial with both single-centre and multicentre arm conducted in close synergy with concurrent trials APPendicitis ACuta II (APPAC II) (per oral (p.o.) vs intravenous+p.o. antibiotics,NCT03236961) and APPAC III (double-blind trial placebo vs antibiotics,NCT03234296) randomised clinical trials. Based on the enrolment for these trials, patients with CT-confirmed uncomplicated acute appendicitis are recruited also to the MAPPAC study. In addition to these conservatively treated randomised patients with uncomplicated acute appendicitis, MAPPAC will recruit patients with uncomplicated and complicated appendicitis undergoing appendectomy. Rectal and appendiceal swabs, appendicolith, faecal and serum samples, appendiceal biopsies and clinical data are collected during the hospital stay for microbiological and immunological analyses in both study arms with the longitudinal study arm collecting faecal samples also during follow-up up to 12 months after appendicitis treatment.Ethics and disseminationThis study has been approved by the Ethics Committee of the Hospital District of Southwest Finland (Turku University Hospital, approval number ATMK:142/1800/2016) and the Finnish Medicines Agency. Results of the trial will be published in peer-reviewed journals.Trial registration numberNCT03257423

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EFFECTIVENESS AND TOLERABILITY OF CV-3988, A SELECTIVE PAF ANTAGONIST, AFTER INTRAVENOUS ADMINISTRATION TO MAN

10.1055/s-0038-1642878 ◽

1987 ◽

Author(s):

J Arnout ◽

A Van Hecken ◽

I Delepeleire ◽

Y Miyamoto ◽

I Holmes ◽

...

Keyword(s):

Light Transmission ◽

Platelet Rich Plasma ◽

Biological Activities ◽

Wide Spectrum ◽

Platelet Activating Factor ◽

Controlled Study ◽

Dependent Manner ◽

Double Blind ◽

Health And Disease

Platelet activating factor (PAF) is a naturally occurring phospholipid with a wide spectrum of biological activities. Although PAF has been ascribed a potential role in various conditions including inflammation, asthma, glomerulonephritis and thrombosis, its precise function in physiologic/pathophysiologic processes remains unclear. The introduction of selective PAF receptor antagonists could represent a useful tool to extend our knowledge of the role of this mediator in health and disease.We have investigated the efficacy and tolerability of (RS)-2-methoxy-3-(octadecylcarbomoyloxy)propy1 2-(3-thiazolio)-ethyIphosphate (CV-3988, Takeda Chem. Ind), a selective PAF antagonist with structural analogies with PAF, after intravenous infusion in man in a double-blind, placebo-controlled study. The compound, in doses from 750 to 2,000 pg/kg, significantly reduced platelet sensitivity to PAF. The threshold aggregating concentration (TAC) of PAF was defined as the minimal concentration causing an irreversible aggregation with a maximal amplitude of at least 50% of the difference in light transmission between platelet rich plasma and platelet poor plasma. It increased in a dose-dependent manner reaching 3.6 times the basal TAC (p<0.0005) at the end and 2.60 times the basal TAC (p<0.0005) 4 hours after infusion of the highest dose. The TAC of PAF returned to the basal value within 24 hours after the end of the infusion.CV-3988 did not cause major side effects nor changes in blood pressure, pulse or respiratory rate. However, small but clinically insignificant changes in plasma haemoglobin and serum haptoglobin were seen at the end and four hours after the end of the infusion, indicating a slight haemolysis probably by high local concentrations at the infusion site.Our results indicate that, when adequate infusion volumes and infusion rates are used, CV-3988 can be safely administered to man and should be useful in elucidating the role of PAF in health and disease.

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Role of anal dilatation in treatment of idiopathic constipation in children: long-term follow-up of a double-blind randomized controlled study

Pediatric Surgery International ◽

10.1007/s00383-004-1336-y ◽

2005 ◽

Vol 21 (2) ◽

pp. 100-105 ◽

Cited By ~ 13

Author(s):

Alireza S. Keshtgar ◽

Harry C. Ward ◽

Graham S. Clayden ◽

Ahmad Sanei

Keyword(s):

Randomized Controlled Study ◽

Controlled Study ◽

Anal Dilatation ◽

Double Blind ◽

Idiopathic Constipation ◽

Randomized Controlled ◽

Long Term Follow Up

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Recent developments in the psychopharmacology of social phobia

Acta Neuropsychiatrica ◽

10.1017/s0924270800033822 ◽

1993 ◽

Vol 5 (4) ◽

pp. 76-82

Author(s):

Den J.A. Boer ◽

I.M. Van Vliet ◽

H.G.M. Westenberg

Keyword(s):

Social Anxiety ◽

Social Phobia ◽

Research Effort ◽

Beta Blockers ◽

Controlled Study ◽

Social Avoidance ◽

Double Blind ◽

Compulsive Disorder ◽

Serotonergic Drugs

SummaryThe last two decades have witnessed an upsurge in the interest in anxiety disorders. Much research effort has been dedicated to panic disorder and obsessive compulsive disorder. However, it is only very recently that we have begun to understand some of the basic principles about the psychopharmacology of social phobia. Drug classes so far studied include beta-blockers, non-selective and irreversible MAO-inhibitors (MAOI's) and benzodiazepinen. Beta-blockers appear to be of use in specific social phobias, like public speaking. There is considerable evidence suggesting that MAOI's are effective in reducing both social anxiety as well as social avoidance. A disadvantage of the conventional irreversible MAOI's is their risk for hypertensive crises when combined with dietary tyramine.So far only a small number of studies with selective MAOI-A inhibitors such as moclobemide and brofaromine have been conducted in social phobia, and the results indicate that both compounds are effective.Drugs exerting selective and specific actions on certain components of e.g. the serotonergic system can now be studied and it is hoped that the role of serotonin and other neuronal systems in social phobia can be elucidated.In order to gain more information about selective serotonergic drugs the first double blind placebo-controlled study with fluvoxamine in social phobia is here reported. Preliminary results indicate a reduction of social anxiety.Finally the role of peptides in the treatment of social phobia is critically reviewed. The MSH/ACTH analog Org 2766 was investigated in patients suffering from social phobia. No anxiolytic effects of this peptide could be observed.

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