Conducting and analyzing clinical studies of cough and cold medications is challenging due to the rapid onset and short duration of the symptoms. The use of Internet-based surveillance tools is a new ...approach in clinical studies that is gradually becoming popular and may become a useful method of recruitment. As part of an initiative to assess the safety and efficacy of cough and cold ingredients in children 6-11 years of age, a surveillance program was proposed as a means to identify and recruit pediatric subjects for clinical studies.
The objective of the study was to develop an Internet-based surveillance system and to assess the feasibility of using such a system to recruit children for common cold clinical studies, record the natural history of their cold symptoms, and determine the willingness of parents to have their children participate in clinical studies.
Healthy potential subjects were recruited via parental contact online. During the 6-week surveillance period, parents completed daily surveys to record details of any cold symptoms in their children. If a child developed a cold, symptoms were followed via survey for 10 days. Additional questions evaluated the willingness of parents to have their children participate in a clinical study shortly after onset of symptoms.
The enrollment target of 248 children was reached in approximately 1 week. Children from 4 distinct geographic regions of the United States were recruited. Parents reported cold symptoms in 163 children, and 134 went on to develop colds. The most prevalent symptoms were runny nose, stuffed-up nose, and sneezing. The most severe symptoms were runny nose, stuffed-up nose, and sore/scratchy throat. The severity of most symptoms peaked 1-2 days after onset. Up to 54% of parents expressed willingness to bring a sick child to a clinical center shortly after the onset of symptoms. Parents found the Internet-based surveys easy to complete.
Internet-based surveillance and recruitment can be useful tools to follow colds in children and enroll subjects in clinical studies. However, study designs should account for a potentially high dropout rate and low rate of adherence to study procedures.
Objective: To quantify the rate of adverse events reported with naproxen compared with placebo, ibuprofen and acetaminophen at non-prescription doses in multiple-dose, multi-day (7-10 days) duration ...clinical trials and further contribute towards current knowledge regarding the safety profile of naproxen.
Methods: Safety data were retrospectively collected from eight randomized, controlled trials that included subjects exposed to a fixed dosing regimen of 220-750 mg naproxen per day over 7-10 days. All data on adverse events and their duration, severity and possible relationship to the study drug were taken from the clinical study reports. The data were used in a post-hoc pooled analysis of participants exposed to naproxen 220-750 mg/day (N = 1494) and grouped according to age (<65 and ≥65 years), daily dose, race and gender.
Results: The safety profile of naproxen closely resembled that of placebo, with similar rates of adverse events across treatment groups as the active comparators. There was no dose effect of naproxen, and there were no differences in older versus younger participants. Most events were mild to moderate. The most frequently reported adverse events in all groups were related to the gastrointestinal system (most commonly dyspepsia with naproxen), with no differences between groups.
Conclusions: Our pooled analysis did not find an increased risk of adverse events with short-term use of non-prescription doses of naproxen compared with placebo, or compared to other common analgesics.
Two studies evaluated the efficacy and safety of a single dose of naproxen sodium 440 mg (NS) compared to the combination of acetaminophen 600 mg and codeine phosphate 60 mg (AC) in subjects with ...postoperative dental pain.
The two studies were single center, randomized, double-blind and double-dummy trials. In both studies, subjects were randomized into one of the following three treatments in a 2:2:1 ratio, respectively: NS, AC, or placebo (PBO). Subjects were administered study medication when they had at least moderate pain following the surgical removal of three or four impacted molars, at least one of which was a mandibular partial or complete bony impaction. Efficacy assessments were completed over an 8-hour evaluation period. The co-primary efficacy assessments in both studies were time-weighted sum of categorical pain intensity differences over 4 hours (SPID4) and time-weighted sum of pain relief scores over 4 hours (TOTPAR4). Other efficacy assessments such as summed scores over 8 hours, time to onset of relief, time to rescue medication and global rating of medication were also assessed.
In Study 1, there were 225 subjects evaluated for efficacy, and 228 evaluated for safety. In Study 2, there were 230 subjects evaluated for efficacy and safety. In both studies, NS and AC were significantly better than placebo for almost all efficacy measures. In Study 1, NS was significantly superior to AC for all summed efficacy scores over 4 and 8 hours except for SPID4. NS was also superior to AC for most individual time point scores from 3 through 8 hours, as well as for the time to taking rescue medication. Both actives had a similar onset of effect. The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO. The most frequently reported AEs with AC were gastrointestinal (GI) and nervous system events. In Study 2, there were no statistically significant differences between the two active treatments for any summed efficacy score, except for TOTPAR8, where NS was significantly better than AC. NS was significantly better than AC for individual pain relief time point scores from 3 through 8 hours and significantly better for individual pain intensity difference scores from 5 through 8 hours. AC had a significantly faster onset of effect compared to NS, but NS had a significantly longer time to rescue compared to AC. Nervous system AEs (dizziness and somnolence) were reported significantly more frequently with AC compared to NS. In conclusion, Both NS and AC are effective in the relief of postoperative dental pain. NS provided comparable to superior relief vs. AC and its analgesic effects lasted significantly longer. NS was well tolerated and resulted in a lower rate of AEs than AC.
In 2017, the US Department of Human Health Services declared a public health emergency to address the national opioid crisis. Since dentists are among the most common specialty groups prescribing opioids, these studies show that NSAIDs (such as naproxen sodium) are effective analgesics for relieving postoperative pain.
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medications in mild-to-moderate acute pain. However, comparative data regarding the duration of analgesia for ...commonly-used NSAIDs at non-prescription doses is lacking. This study evaluated the time to rescue medication following a single dose of naproxen sodium (NAPSO) vs ibuprofen (IBU) and placebo in subjects with moderate-to-severe post-surgical dental pain.
Methods: This single-center, randomized, double-blind, parallel group, placebo-controlled study included healthy subjects with moderate-to-severe baseline pain (Categorical Pain Intensity Scale) who also rated their pain ≥ 5 on a 0-10 pain intensity Numerical Rating Scale following extraction of two impacted mandibular third molars. A single oral dose of NAPSO (440 mg), IBU (400 mg), or placebo was administered. The primary efficacy endpoint was the time to first rescue medication, while secondary endpoints included the sum of pain intensity difference (SPID) and total pain relief (TOTPAR) over 24 h. ClinicalTrials.gov trial registration number: NCT03404206 (EudraCT 2017-005049-67).
Results: In the per protocol population (n = 385; mean age = 19 years), the time to rescue medication was significantly (p < .001) longer with NAPSO than IBU and placebo. After treatment, the greatest separation of NAPSO from IBU occurred at 9-14 h and from placebo at 1-6 h. Fewer NAPSO subjects required rescue medication (58/166, 34.9%) compared with IBU (137/165, 83.0%) and placebo (44/54, 81.5%). SPID 0-24 h and TOTPAR 0-24 h were both greater with NAPSO than IBU or placebo.
Conclusions: The duration of pain relief after a single dose of NAPSO was significantly longer than after IBU, and significantly fewer NAPSO-treated subjects required rescue medication over a 24-h period.
Trial registration:
ClinicalTrials.gov identifier: NCT03404206.
Opioid/acetaminophen combinations may be overly prescribed in many post-surgical situations where a non-steroidal anti-inflammatory drug with equal or greater efficacy, fewer central nervous system ...side effects, and no risk for opioid abuse could be substituted. We compared a single, non-prescription dose of naproxen sodium 440 mg (NapS) against hydrocodone plus acetaminophen 10/650 mg (HYD+APAP) in post-impaction surgery pain.
Single-center, randomized, double-blind, placebo-controlled study in moderate-severe pain after surgical removal of impacted third molars (ClinicalTrials.gov: NCT04307940). Patients (n = 212) received NapS, HYD+APAP, or placebo and were assessed over 12 hours. Primary endpoint: summed pain intensity difference from 0 to 12 hours (SPID
0-12
). Secondary endpoints: pain intensity, pain relief, time to rescue medication, duration of pain at least half gone. Others: onset of pain relief, global assessment of treatment, adverse events.
All 221 randomized patients formed the safety population and were included in the intention-to-treat sensitivity analysis. Nine patients discontinued treatment or had protocol violations, and 212 patients were included in the per-protocol, primary efficacy population. Both active treatments were significantly more effective than placebo. NapS was significantly more effective than HYD+APAP regarding SPID
0-12
(p = 0.01; primary endpoint), total pain relief (0-6 and 0-12 hours; p < 0.05), time to rescue medication (p < 0.001), and duration of pain at least half gone (p < 0.001). HYD+APAP was not statistically superior to NapS for any endpoint. More adverse events were reported with HYD+APAP (n = 63) than NapS (n = 2) and placebo (n = 20), including nausea, vomiting, and dizziness.
In moderate-to-severe postsurgical dental pain, a single dose of NapS was at least as effective as HYD+APAP in the early hours, significantly more effective at reducing pain intensity and providing greater pain relief over 12 hours, and was better tolerated. When not contraindicated, NapS should be considered a preferred alternative to opioid combinations for acute pain. (ClinicalTrials.gov, Identifier: NCT04307940;
https://clinicaltrials.gov/ct2/show/NCT04307940
)
Objectives: Current osteoarthritis therapies aim to alleviate pain and maintain joint function. Non-prescription oral non-steroidal anti-inflammatory drugs are frequently used alone for pain relief ...in osteoarthritis. This post-hoc pooled analysis evaluated the analgesic efficacy and safety of two non-prescription doses of naproxen sodium for short-term use in patients with osteoarthritis of the knee or hip. A separate sub-group analysis of older patients who were administered a lower dose of naproxen sodium was performed.
Methods: In four multi-center, multi-dose, randomized, parallel, double-blind, placebo-controlled studies, oral naproxen sodium (age-based dosing regimen: <65 years, 660 mg/day; ≥65 years, 440 mg/day) or placebo was administered over 7 days. Data at baseline and after 7 days in 818 patients who received naproxen sodium or placebo (n = 409 in each group) was pooled and analyzed. Five-point rating scales were used to assess knee or hip joint pain, stiffness after rest, day and night pain, and patient and investigator assessment of treatment, while function was evaluated using a timed 50-foot walk test.
Results: Compared with placebo, there were significant improvements in pain and physical function with naproxen sodium (p < .05), and treatment was rated "good" to "excellent" significantly more often (p < .001) by investigators and patients. Efficacy results were similar among younger and older patients. There were no significant differences in adverse events between groups, regardless of age.
Conclusions: For the acute management of underlying pain in patients with moderate osteoarthritis of the hip or knee, non-prescription naproxen sodium is effective and well tolerated in patients of all ages.
Aspirin is the dominant antiplatelet therapy for cardiovascular disease. Naproxen is frequently used in aspirin-treated patients and may influence the antiplatelet effect of aspirin. We evaluated the ...pharmacodynamic interaction (lower bound of the one-sided 95% CI for serum TxB
2
inhibition < 95%) between 220 mg immediate-release naproxen sodium (once or twice daily) and 81 mg daily immediate release aspirin at various dosing intervals. There was no interaction during the first day of concurrent treatment. After 10 days, irrespective of the timing and dose of naproxen in relation to aspirin dosing, a pharmacodynamic interaction occurred which persisted after discontinuing naproxen. In the control group (aspirin alone), the lower bound for serum TxB
2
inhibition was > 98% at all time points. The clinical relevance of these observations remains unknown and merits further investigation since over-the-counter naproxen is widely used to relieve pain by individuals taking low dose aspirin for cardioprotection.
Clinical Trial Registration: NCT02229461
The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double‐blind study in 36 Japanese subjects who complained of cold ...and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 × a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by ail 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks’examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.
Pain, swelling, loss of function, and hyperthermia are acute postoperative sequelae of inflammation due to tissue injury during surgical procedures. Pharmacologic strategies for minimizing the ...clinical manifestations of surgical trauma are often directed toward blocking the formation or inhibiting the effects of the biochemical mediators of acute inflammation. This study compared two nonsteroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ibuprofen, with a prototype glucocorticoid, methylprednisolone, in two replicate placebo-controlled studies for suppression of inflammation due to the surgical removal of impacted third molars. The results indicate that NSAIDs produce greater initial analgesia than do steroids, whereas steroids result in greater suppression of swelling and less loss of function. Examination of the pooled data from the two studies indicates that NSAID pretreatment results in a modest suppression of swelling in comparison with placebo. These data suggest that the acute analgesic effects of NSAIDs in the oral surgery model are due to suppression of a nociceptive process, presumably prostaglandin formation, rather than a generalized anti-inflammatory effect.
Release of β‐endorphin is modulated by physiologic stress and a variety of hormonal and pharmacologic factors. Prostaglandin E2 inhibits release of β‐endorphin and corticotropin from pituitary ...corticotroph cells, suggesting that suppression of prostaglandin levels should increase β‐endorphin release. This hypothesis was tested by administration of 600 mg ibuprofen before surgical stress in humans in comparison to placebo and methylprednisolone. Plasma samples were analyzed for immunoreactive β‐endorphin with concurrent measurement of pain and apprehension. Levels of immunoreactive β‐endorphin increased during surgery in the placebo group but were significantly greater in the group of patients pretreated with ibuprofen. Methylprednisolone suppressed intraoperative immunoreactive β‐endorphin, compared with both placebo and ibuprofen. Parallel in vivo and in vitro studies indicate that nonsteroidal anti‐inflammatory drug potentiation of endorphin release is mediated at the level of the pituitary corticotroph cell. These results show that ibuprofen enhances pituitary release of β‐endorphin by corticotroph cells in response to stress.
Clinical Pharmacology & Therapeutics (1997) 62, 74–81; doi:
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