Early vs. Non-Early Intervention in Acute Migraine — ‘Act When Mild (AwM)’. A Double-Blind, Placebo-Controlled Trial of Almotriptan

The study was designed to compare the response to almotriptan in migraine patients who take medication early in the course of the attack with that when medication is taken after pain has become moderate or severe. A randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) comparing treatment administration when pain intensity was mild and within 1 h of headache onset vs. pain that had become moderate or severe was conducted. Of 491 migraineurs enrolled, 403 were evaluable [intention-to-treat population (ITT)]. Their mean age was 38 years, 84% were female and they had a mean of 3.7 attacks/month. Of these patients, 10% did not take medication according to their randomly allocated basal pain intensity (mild or moderate/severe) and were subsequently reassigned to that group for this analysis —'Act when Mild (AwM)' group. In the almotriptan arms, 53% of mild basal pain and 38% of moderate/severe basal pain patients were pain free at 2 h ( P = 0.03; primary end-point). Corresponding proportions in the placebo groups were 25% and 17% (statistically significant vs. respective almotriptan arms). Secondary end-points (ITT) were also significantly in favour of early intervention with almotriptan, both between and across treatment groups, such as sustained pain free: 45.6% vs. 30.5% ( P = 0.02). Adverse events were reported in < 5% of treated patients in all groups (NS), with no serious events. Treatment with almotriptan while migraine pain is still mild provides statistically significant and clinically relevant enhancements in efficacy compared with treatment when pain has reached higher severity levels.

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The ‘Act When Mild’ (AwM) Study: A Step Forward in Our Understanding of Early Treatment in Acute Migraine

Cephalalgia ◽

10.1111/j.1468-2982.2008.01689.x ◽

2008 ◽

Vol 28 (2_suppl) ◽

pp. 36-41 ◽

Cited By ~ 30

Author(s):

PJ Goadsby

Keyword(s):

Pain Intensity ◽

Group Treatment ◽

Controlled Trial ◽

Evidence Base ◽

Primary Outcome Measure ◽

Double Blind ◽

Intention To Treat ◽

Severe Stage ◽

Headache Onset ◽

Severe Group

An important issue in the management of migraine is the advice given to patients as to when to take their treatment in the course of the attack. While it seems common sense almost to take treatment early in the attack, the evidence base for that advice is not as robust as could be expected. The ‘Act when Mild’ (AwM) Study was a randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after administration of treatment when pain intensity was mild and within 1 h of headache onset (mild/early) with outcomes when pain had become moderate or severe. Of 491 migraineurs enrolled, 403 were evaluable with an intention-to-treat population (ITT) of 404. At the primary end-point, 2 h pain free, on the ITT analysis 49% of patients in the almotriptan 12.5 mg treat early/mild group and 40% in the treat moderate/severe group had responded ( P = 0.21). Of these patients, 43 did not take medication according to their randomly allocated baseline pain intensity (mild or moderate/severe) and were subsequently reassigned, prior to study unblinding, to the appropriate group (AwM population) for re-analysis of the primary outcome measure: 2-h pain-free rates. In the almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe group were pain free at 2 h ( P = 0.02; AwM population). The corresponding proportions in the placebo groups were 24.7% and 17.5% (significantly lower than the respective almotriptan arms; P ≤ 0.01). Considering the ITT population, secondary end-points were also significantly in favour of treatment with almotriptan in the mild/early vs. the moderate/severe stage, including: sustained pain-free, 45.6% vs. 30.5% ( P = 0.02); headache recurrence at 24 h, 6% vs. 24% ( P = 0.0124). Adverse events were reported in < 5% of patients, with no significant differences between almotriptan and placebo and no serious events in any group. Treatment with almotriptan while migraine pain is still mild and within 1 h of onset provides statistically significant and clinically relevant enhancements in efficacy compared with waiting until pain has reached higher severity levels.

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Relief of pain and trismus in patients treated with naproxen or acetylsalicylic acid after tonsillectomy

The Journal of Laryngology & Otology ◽

10.1017/s0022215100103913 ◽

1988 ◽

Vol 102 (1) ◽

pp. 39-42 ◽

Cited By ~ 5

Author(s):

S. Kristensen ◽

K. Tveteraas ◽

P. Hein ◽

H. B. Poulsen ◽

K. E. Outzen

Keyword(s):

Clinical Trial ◽

Acetylsalicylic Acid ◽

Pain Intensity ◽

Sleep Disturbances ◽

Significant Positive Correlation ◽

Controlled Trial ◽

Double Blind ◽

Treatment Groups ◽

Significant Difference ◽

Therapeutic Gain

AbstractThe pain-relieving efficacy of naproxen and acetylsalicylic acid (ASA) in tonsillectomized patients was compared in a double blind parallel clinical trial comprising 83 patients, among whom 42 were treated with naproxen and 41 with ASA. The patients were treated post-operatively for two days with either naproxen suppositories 500 mg. twice, or ASA effervescent tablets 1000 mg. three times, daily.The therapeutic gain was evaluated by recording the intensity of pain, reduced ability to open the mouth (trismus), consumption of supplementary analgesic (parcetamol), and pain-related sleep disturbances.The statistical analysis of the results revealed no differences in pain intensity, consumption of additional analgesics or pain-related sleep disturbances in the two treatment groups. A considerable degree of trismus was demonstrated in most of the tonsillectomized patients. This reduced ability to open the mouth was gradually overcome in the naproxen group while it remained unchanged in the ASA group, however, no statistical significant difference could be demonstrated. Additionally, no significant positive correlation between pain intensity and trismus was proven. The pain-relieving effect, however, was unsatisfactory in both the naproxen and the ASA group, and clinical controlled trial studies of alternative analgetics in tonsillectomized patients are still to be encouraged.

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Efficacy and tolerance of early administration of tranexamic acid in patients with cirrhosis presenting with acute upper gastrointestinal bleeding: a study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (the EXARHOSE study)

BMJ Open ◽

10.1136/bmjopen-2018-021943 ◽

2018 ◽

Vol 8 (8) ◽

pp. e021943 ◽

Cited By ~ 3

Author(s):

Matthieu Heidet ◽

Roland Amathieu ◽

Etienne Audureau ◽

Oriane Augusto ◽

Violaine Nicolazo de Barmon ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Tranexamic Acid ◽

Upper Gastrointestinal Bleeding ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Intention To Treat ◽

Acute Upper Gastrointestinal Bleeding ◽

Shunt Procedure ◽

Upper Gastrointestinal

IntroductionThe management of acute upper gastrointestinal bleeding (UGIB) is challenging in patients with cirrhosis, as it is responsible for severe complications and high mortality rates. Tranexamic acid (TXA) may help control the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still, there is a lack of unbiased data to conclude on its efficacy. The aim of this study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in patients with cirrhosis.Methods and analysisThis study is a multicentre, randomised, double-blind, placebo-controlled trial, for adult patients with cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or placebo (saline). Physicians from emergency mobile services, emergency departments (EDs) or intensive care units (ICUs) can include patients. Besides study intervention, standard care for UGIB will be performed as recommended. Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or saline, immediately followed by three identical intravenous infusions over 8 hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main analyses will be conducted in intention to treat on every patient included, then in modified intention to treat on patients with underlying lesion of portal hypertension visualised by endoscopy. The main objective is to show efficacy of TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes and mortality). Secondary objectives aim at showing the efficacy of TXA on each individual component of the main outcome measure and others at 6 weeks and later (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific complications, length of stay in ICU and in hospital, safety and tolerance of TXA, liver transplantation). Included patients will be followed up to 1 year after inclusion.500 patients will be necessary to show a reduction in the prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of 5% and a power of 80%.Ethics and disseminationEthical approval has been obtained from the Comité de Protection des Personnes Ile-de-France 1 (CPP-IDF1). Results will be disseminated via publications in peer-review medical journals and scientific forums.Protocol versionThis protocol is based on the latest version, as established on 11 October 2017 and validated by the IRB CPP Ile-de-France 1.Trial registration numberNCT03023189.

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Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/201592 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Tsuyoshi Miyaoka ◽

Motohide Furuya ◽

Jun Horiguchi ◽

Rei Wake ◽

Sadayuki Hashioka ◽

...

Keyword(s):

Placebo Group ◽

Controlled Trial ◽

Controlled Study ◽

Efficacy And Safety ◽

Treatment Resistant ◽

Double Blind ◽

Double Blind Placebo ◽

Intention To Treat ◽

The Difference ◽

The Individual

Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan) in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted.Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS) and intention-to-treat (ITT). However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54:−0.23±0.08; placebo:−0.03±0.08,P<0.018), tension (TJ-54:−0.42±0.09; placebo:−0.18±0.09,P<0.045), and poor impulse control (TJ-54:−0.39±0.10; placebo:−0.07±0.10,P<0.037).Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

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A randomized, double-blind, placebo-controlled study to assess the effect of an aqueous extract of Triticum aestivum on canine outer ear inflammation

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2017001100012 ◽

2017 ◽

Vol 37 (11) ◽

pp. 1270-1274 ◽

Cited By ~ 2

Author(s):

Ciciane P.M. Fernandes ◽

Alana Hijano ◽

Charles S. Lima ◽

Eduardo G. Fontoura ◽

Renata C. Schramm ◽

...

Keyword(s):

Aqueous Extract ◽

Bacterial Infections ◽

Elevated Temperatures ◽

Controlled Trial ◽

External Otitis ◽

Controlled Study ◽

Double Blind ◽

Fungal Isolation ◽

Double Blind Placebo ◽

Treatment Groups

ABSTRACT: Outer ear otitis is a multifactorial acute or chronic inflammation of the ear canal, and treatment is often hampered by growing antibiotic resistance. Pre-clinical assessments have shown that an aqueous extract of Triticum aestiveum (wheat) can effectively reduce the symptoms associated with the disease. The purpose of this study was to assess, through a randomized, double-blind, placebo-controlled trial, the use of T. aestivum extract on canine external otitis. Thirty dogs (60 ears) met the criteria to be included in this study, and were randomly assigned a treatment group: placebo, extract, or positive control (C+). Ears were treated every day for seven days, and assessed before treatment (day zero), after treatment (day 7), and again on reassessment (day 14). Clinical assessment included: type of otitis; pinna conformation; presence or absence of itchiness, foul odor, and pain; presence of stenosis, erythema and cerumen. Furthermore, the evaluators assessed the temperature in each ear and the pH of the cerumen, and swabs were collected for bacterial and fungal isolation. All veterinarians treating and assessing the animals were blinded regarding the treatment groups. Results showed little difference in the treatment groups regarding clinical parameters. By day 7 ears treated with the C+ had elevated temperatures, when compared to the others (P<0.05), this was still true on day 14. Bacterial isolation had completely died out by day 7, however, on day fourteen the placebo group had six ears with bacterial infections, unlike the other two groups (P<0.05). The results generated herein show that a 25% wheat extract solution is effective in the reduction of clinical and microbiological parameters of external otitis, with better results when compared to a placebo, and similar results to the traditional, antibiotic/anti-inflammatory treatment.

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Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial

Trials ◽

10.1186/s13063-021-05776-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Karin Due Bruun ◽

Kirstine Amris ◽

Henrik Bjarke Vaegter ◽

Morten Rune Blichfeldt-Eckhardt ◽

Anders Holsgaard-Larsen ◽

...

Keyword(s):

Pain Intensity ◽

Low Dose ◽

Controlled Trial ◽

Muscle Performance ◽

Double Blind ◽

Intention To Treat ◽

Average Pain Intensity ◽

Average Pain ◽

Secondary Outcomes ◽

Low Dose Naltrexone

Abstract Background Low-dose naltrexone (LDN) is used widely as an off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with a high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last 7 days in women with fibromyalgia. Methods A single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a 4-week titration phase. The primary outcome is change in average pain intensity (during the last 7 days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e., tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers. Discussion This study will contribute with high-level evidence on the efficacy of low-dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia. Trial registration EudraCT 2019-000702-30. Registered on 12 July 2019. ClinicalTrials.gov NCT04270877. Registered on 17 February 2020

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Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01794-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 28

Author(s):

Julie H. Ishida ◽

Anita Patel ◽

Aneesh K. Mehta ◽

Philippe Gatault ◽

Jacqueline M. McBride ◽

...

Keyword(s):

High Risk ◽

Kidney Transplant ◽

Controlled Trial ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cmv Infection ◽

Double Blind ◽

Double Blind Placebo ◽

Treatment Groups ◽

Cmv Disease

ABSTRACT Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R−) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and 35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%; P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum-adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030). Adverse events were generally balanced between treatment groups. In high-risk kidney transplant recipients, RG7667 was well tolerated, numerically reduced the incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to CMV viremia, and was associated with less CMV disease than the placebo. (This study has been registered at ClinicalTrials.gov under registration no. NCT01753167.)

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Low dose naltrexone for the treatment of fibromyalgia: Protocol for a double-blind, randomized, placebo-controlled trial

10.21203/rs.3.rs-401663/v1 ◽

2021 ◽

Author(s):

Karin Due Bruun ◽

Kirstine Amris ◽

Henrik Bjarke Vaegter ◽

Morten Rune Blichfeldt-Eckhardt ◽

Anders Holsgaard-Larsen ◽

...

Keyword(s):

Pain Intensity ◽

Low Dose ◽

Controlled Trial ◽

Muscle Performance ◽

Double Blind ◽

Intention To Treat ◽

Average Pain Intensity ◽

Average Pain ◽

Secondary Outcomes ◽

Low Dose Naltrexone

Abstract Background Low dose naltrexone (LDN) is used widely as off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last seven days in women with fibromyalgia.Methods A single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years and diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a four-week titration phase. The primary outcome is change in average pain intensity (during the last seven days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e. tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers.Discussion This study will contribute with high-level evidence on the efficacy of low dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia.Trial registration: EudraCT number 2019-000702-30 (registered on 2019-07-12). ClincalTrials.gov Identifier: NCT04270877 (registered on 2020-02-17).

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Double-Blind, Placebo-Controlled, Randomized Study of Eicosapentaenoic Acid Diester in Patients With Cancer Cachexia

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.5724 ◽

2006 ◽

Vol 24 (21) ◽

pp. 3401-3407 ◽

Cited By ~ 180

Author(s):

Kenneth C.H. Fearon ◽

Matthew D. Barber ◽

Alastair G. Moses ◽

Sam H. Ahmedzai ◽

Gillian S. Taylor ◽

...

Keyword(s):

Eicosapentaenoic Acid ◽

Cancer Cachexia ◽

Controlled Trial ◽

Randomized Study ◽

Single Agent ◽

Diethyl Ester ◽

Double Blind ◽

Double Blind Placebo ◽

Intention To Treat ◽

Combination Regimens

Purpose Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Patients and Methods Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. Results The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4g EPA (−0.9 kg to 1.5 kg). Conclusion The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens.

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Homeopathic treatment of migraine: A double blind, placebo controlled trial of 68 patients

British Homeopathic Journal ◽

10.1054/homp.1999.0332 ◽

2000 ◽

Vol 89 (01) ◽

pp. 4-7 ◽

Cited By ~ 32

Author(s):

P Straumsheim ◽

C Borchgrevink ◽

P Mowinckel ◽

H Kierulf ◽

O Hafslund

Keyword(s):

Pain Intensity ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

Attack Frequency ◽

Double Blind ◽

Double Blind Placebo ◽

Homeopathic Treatment ◽

Registration Period ◽

Significant Difference ◽

Accompanying Symptoms

AbstractTo evaluate the efficacy of homeopathy in preventing migraine attacks and accompanying symptoms, a randomised, double-blind, placebo-controlled clinical trial was conducted. There was a one-month registration period without treatment, followed by four months individualised homeopathic treatment or identical placebo. Patients were stratified for common or classical migraine.Seventy-three patients were randomised, 68 completed the trial. Baseline values were similar in the two groups. Both the homeopathy and placebo groups had reduction in attack frequency, pain intensity and drug consumption, with a statistically non-significant difference favouring homeopathy. Migraine diaries showed no difference between groups. The neurologists’ trial evaluation showed a statistically significant reduction in attack frequency in the homeopathy group (P=0.04) and non-statistically significant trends in favour of homeopathy for pain intensity and overall evaluation.Further research, with improved trial design, on the possible role of homeopathy in migraine prophylaxis is justified.

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