Ipratropium nasal spray: a new treatment for rhinorrhea in the common cold. Common cold and high-dose ipratropium bromide: use of anticholinergic medication as an indicator of reflex-mediated hypersecretion. Ipratropium bromide treatment of experimental rhinovirus infection. Effectiveness and safety of intranasal ipratropium bromide in common colds. A randomized, double-blind, placebo-controlled trial. A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold. Efficacy and safety of topical combinations of ipratropium and xylometazoline for the treatment of symptoms of runny nose and nasal congestion associated with acute upper respiratory tract infection. A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.
A need is often present for symptomatic treatment of the common cold. A blocked nose can be opened by a vasoconstrictor, but no effective therapy is known today for rhinorrhea. The aim of the present trial was to study the effect of the topically active parasympatholytic, ipratropium, on rhinorrhea. In a placebo-controlled group comparative trial, 80 micrograms of ipratropium were taken as a nasal spray 4 times daily for 1 wk by 40 adults with spontaneously occurring common colds. All subjects administered an intranasal vasoconstrictor (xylomethazoline, 0.1%) 5 min before administering placebo or ipratropium. Ipratropium treatment resulted in a significant reduction in nasal discharge compared with that of placebo treatment during the whole treatment period (p less than 0.001), but the drug was especially effective the first 3 days, when the watery secretion was predominant. It was concluded that this new spray can be of value in the first days of a cold, when nasal discharge is a nuisance. It was our aim to study the role played by parasympathetic reflexes for the amount and physical characteristics of nasal discharge during a common cold, and to define the maximum anti-rhinorrhoea effect obtainable with anticholinergic medication. Fifty adults with naturally acquired colds were treated with a very high dose of the topically active cholinoceptor-antagonists ipratropium bromide in a randomized, double-blind, placebo-controlled study of parallel groups. A dosage of 400 micrograms was given 4 times daily for 3 days, using a specially manufactured high-dosed pressurized aerosol. This treatment resulted in a 56% reduction in the number of nose blowings (p < 0.01) and a 58% reduction in the weight of blown secretions (p < 0.01). Assessment of the "pourability" of the nasal discharge indicated that ipratropium bromide mainly reduces the watery secretions but not the mucopurulent secretions. The high dose of ipratropium bromide caused nose- and mouth-dryness in a considerable number of the patients. In conclusion: (1) during the first days of a common cold about 60% of the nasal discharge is a reflex-mediated product from nasal glands; (2) this type of secretion is predominantly watery; and (3) ipratropium bromide can reduce watery rhinorrhoea in the common cold, but a lower dose is required in order to avoid side effects. The importance of parasympathetic-cholinergic mechanisms in the production of common cold symptoms is not clear. The quaternary ammonium anticholinergic antagonist ipratropium bromide was intranasally administered under double-blind, randomized, placebo-controlled conditions to assess its tolerance and efficacy in reducing nasal hypersecretion in adult volunteers with experimental rhinovirus colds. Ipratropium was sprayed intranasally three times daily (80 micrograms per treatment) for 5 days beginning 24 h after intranasal inoculation of rhinovirus type 39. Clinical colds occurred in 50% of 30 infected ipratropium recipients and in 76% of 33 infected placebo recipients (P = 0.04). The nasal mucus weights tended to be lower for ipratropium-treated persons (mean +/- standard deviation, 14.7 +/- 15.1 g/5 days) than for placebo-treated recipients (24.7 +/- 28.0 g/5 days; P = 0.076). Whereas total nasal symptom scores were similar between the two groups, the rhinorrhea score analyzed for each day of treatment showed nonsignificant trends favoring the ipratropium group over the last 4 days of treatment. Ipratropium was generally well tolerated. The results suggest that cholinergic mechanisms are at least partially responsible for nasal mucus production in rhinovirus colds but that the effect of anticholinergic compounds alone is insufficient to be of practical use in treatment, although they may have value as components of multi-ingredient preparations. To determine the tolerability and clinical effectiveness of intranasal ipratropium bromide for the treatment of symptoms of common colds.
                Multicenter, double-blind, randomized trial.
                3 university student health services.
                411 previously healthy persons 14 to 56 years of age who had cold symptoms that had lasted for no more than 36 hours, rhinorrhea subjectively judged to be of at least moderate severity, and documented nasal discharge of at least 1.5 g over a 1-hour observation period.
                Either 1) ipratropium bromide nasal spray 0.06% in buffered salt solution, two 42-micrograms sprays per nostril administered by metered pump spray; 2) control nasal spray, which consisted of buffered salt solution; or 3) no treatment. Treatments were self-administered three or four times daily during waking hours for 4 days. After receiving their morning dose, patients stayed at the study center for 6 hours on study day 1 and 3 hours on study day 2; symptom severity was recorded and nasal mucus discharges were collected and weighed hourly during these periods.
                Ipratropium recipients had 26% less nasal discharge than controls (P = 0.0024) and 34% less nasal discharge than untreated patients (P = 0.0001). Severity of rhinorrhea as judged subjectively was reduced in ipratropium recipients by 31% compared with controls and by 78% compared with untreated patients (P = 0.0001 for both comparisons). In addition to being associated with reductions in daily assessments of the severity of rhinorrhea (P < or = 0.003), ipratropium was associated with reduced sneezing on study days 2 (20% difference; P = 0.03) and 4 (30% difference; P = 0.02) but not with reduced nasal congestion compared with the control spray. Ipratropium was generally well tolerated but was associated with higher rates of blood-tinged mucus (16.8% in the ipratropium group compared with 3.6% in the control group; P = 0.01) and nasal dryness (11.7% in the ipratropium group compared with 3.6% in the control group; P = 0.021) than the control spray. Patient assessments of the overall effectiveness of treatment were more favorable for ipratropium than for the control spray (P < or = 0.026) or for no treatment (P < or = 0.002) on each day of inquiry (study days 1, 2, and 5).
                Intranasal ipratropium bromide provides specific relief of rhinorrhea and sneezing associated with common colds. Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in-clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003). Rhinorrhea and nasal congestion are simultaneous symptoms associated with the common cold. This study investigated the efficacy and safety of a combination nasal spray of ipratropium and xylometazoline for simultaneous treatment of these symptoms.
                The trial was a multicenter double-blind, parallel-group, randomized design on patients with common cold symptoms. Patients scored symptoms of runny nose and nasal congestion and recorded adverse events in a diary for up to 7 days. Patients also recorded tissue use. The five test treatments consisted of ipratropium, 0.6 mg/mL, and xylometazoline, 1.0 mg/mL; ipratropium, 0.6 mg/mL, and xylometazoline, 0.5 mg/mL; ipratropium, 0.6 mg/mL; xylometazoline, 1.0 mg/mL; and placebo solution.
                Eight hundred sixty-four patients were screened and 786 patients received treatment. One day after treatment there was a clear separation between the scores for the placebo and ipratropium treatment groups for rhinorrhea and between the placebo and xylometazoline treatment groups for congestion. Both ipratropium/xylometazoline 1.0 and ipratropium/xylometazoline 0.5 treatments were superior to xylometazoline with respect to rhinorrhea (p < 0.0001) and superior to ipratropium with respect to nasal congestion scores (p < 0.001). Both the ipratropium combination treatments had significantly lower tissue use than the xylometazoline treatment group (p < 0.0001). Adverse events were distributed equally between the treatments, except mucus tinged with blood, epistaxis, nasal passage irritation, and nasal dryness, which had a higher incidence in the three groups that received medicines containing ipratropium.
                The results indicate that a combination medicine of ipratropium and xylometazoline is safe and effective for treatment of rhinorrhea and nasal congestion associated with common cold. Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.
For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.