Double-blind group comparative study of 2% nedocromil sodium eye drops with 2% sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis

A 4 week, multicentre, double-blind, double dummy, placebo controlled group comparative study was carried out during the birch pollen season to compare the efficacy and tolerability of 2% nedocromil sodium eye drops (twice daily) and 2% sodium cromoglycate eye drops (four times daily). Participants with a history of seasonal allergic conjunctivitis (SAC) were randomized to receive nedocromil sodium (60), sodium cromoglycate (61) or placebo (64). Clinical assessment of SAC showed improvement with both active treatments compared to placebo but symptomatology was low and only changes in photophobia and grittiness reached significance (P < 0.05). Patient diaries showed significant control of itching by both active treatments, compared to placebo, with no differences between the active preparations. Patients' opinions indicated a marked placebo effect: 73% of this group reported full or moderate control of symptoms, compared with 75% in sodium cromoglycate and 80% in the nedocromil sodium group. Unusual symptoms were most common (27 patients) with nedocromil sodium eye drops: P < 0.05 vs. placebo (15 patients). There were no serious adverse events. Nedocromil sodium eye drops (b.d.) and sodium cromoglycate eye drops (q.i.d.) were both considered clinically more effective than placebo in controlling symptoms of SAC due to birch pollen.     

Nedocromil sodium 2% eye drops for twice-daily treatment of seasonal allergic conjunctivitis: a Swedish multicentre placebo-controlled study in children allergic to birch pollen

This was a multicentre, double-blind, randomized group comparative study in which 77 children, aged 6–16 years, received 2% nedocromil sodium eye drops and 72 received placebo, one drop into each eye twice daily. The treatment period was 4 weeks, covering the peak birch pollen season. Prior to the start or the season, patients who had mended the clinic the previous 2 years because of seasonal allergic conjunctivitis (SAC) to birch pollen, entered a one week baseline period during which symptoms were assessed, diary cards completed, and routine sampling of blood and urine earned out. The double-blind treatment period then commenced at the onset of the birch pollen season. Patients parents kept daily diary record cards of eye symptom severity and concomitant therapy. Conjunctivitis was mild in both treatment groups but nedocromil sodium was more effective than placebo in controlling symptoms. During the 2–3 weeks of peak pollen counts, this therapeutic effect was statistically significant for itching (P <0–01), watering (P <0.05) and total symptom score (P <0.01), but was not significant for grittiness (P= 0.08) or redness (P = 0.06). Global opinions of efficacy showed no difference between treatments, due to a high placebo effect (however, the diary card data indicated a significant improvement with nedocromil sodium). We therefore conclude that nedocromil sodium 2% eye drops, administered twice daily, is an effective treatment for SAC in children.     

Topical levocabastine versus sodium cromoglycate in allergic conjunctivitis

The aim of this study was to evaluate the effect of levocabastine, a new H1-blocking antihistamine for topical use, in comparison with sodium cromoglycate on conjunctival symptoms of birch pollinosis. The two drugs were compared in a randomized double-blind comparative study over 5 weeks in 37 children and adolescents (6-19 years of age) with birch pollen conjunctivitis. Nasal symptoms occurred in 31 of the children and were treated with beclomethasone dipropionate nasal spray. An oral antihistamine was offered as rescue medication for eye symptoms. Initially, the patients received placebo four times a day for a 7-day run-in period. Conjunctival symptoms were recorded daily on diary cards on a 100 mm visual analogue scale. The pollen counts indicated a short but intensive birch pollen season. There was no statistically significant difference between the two treatment groups with regard to eye symptom scores before and during active treatment. However, the patients' evaluation of the efficacy of the therapy was in favour of levocabastine (P less than 0.01). Topical levocabastine, an H1-blocker, applied twice daily, seems to protect from symptoms of allergic conjunctivities as favourably as sodium cromoglycate applied four times a day. There was no difference in number or character of reported adverse reactions between the two treatment groups.     

Double-blind group comparative study of 2% nedocromil sodium eye drops with placebo eye drops in the treatment of seasonal allergic conjunctivitis

A multicenter double-blind group comparative study was carried out in 126 patients, 64 of whom received 2% nedocromil sodium eye drops, and 62 placebo eyedrops twice each day for the treatment of seasonal allergic conjunctivitis to birch pollen. The patients were evaluated at 2 week intervals for clinical signs of conjunctivitis and kept daily diary records of eye symptoms (0-4 severity scales) and concomitant therapy. Diary trends favored active treatment, and reached significance for excessive lacrimation (P less than .05) during peak pollen challenge. Clinic assessments showed the same directional trend and final opinions of treatment efficacy were significantly in favor of nedocromil sodium (P = .003, patients; P = .006, clinicians). In addition, the placebo group used significantly more topical (P less than .05) and oral (P less than .01) concomitant antihistamine therapy. Nedocromil sodium and placebo treatments were equally acceptable and well tolerated. The results show that 2% nedocromil sodium used topically twice each day is an effective therapy for seasonal allergic conjunctivitis.     

Comparative Therapeutic Studies with Tilavist

Comparative clinical trials which include known therapies as well as placebos are essential in constructing a solid basis from which to 'launch' any new drug. This applies especially to eye drops for treatment of seasonal allergic conjunctivitis, where the symptomatology, already dependent on the vagaries of the natural pollen challenge season, is further influenced by a positive washing action of the placebo eye drops. Tilavist (2% nedocromil sodium ophthalmic solution) has therefore been compared with sodium cromoglycate eye drops and non-sedating antihistamine tablets, both mainstays in the treatment of seasonal allergy, in a series of double-masked, placebo-controlled, mainly multicentre studies. Nedocromil sodium, twice or four times daily, proved as effective overall as sodium cromoglycate (2% or 4% four times daily) in three seasonal trials, and was the more effective treatment in a study of patients with vernal keratoconjunctivitis. Its efficacy was most evident during peak periods of pollen challenge, when neither placebo nor sodium cromoglycate eye drops controlled breakthrough symptoms. Three further seasonal studies showed nedocromil sodium eye drops to be as effective as standard oral doses of astemizole and terfenadine, whilst a faster onset of action than terfenadine was reported in one multicentre study.     

A comparison of topical levocabastine and sodium cromoglycate in the treatment of pollen-provoked allergic conjunctivitis

A total of 71 patients with documented birch and grass pollen allergy participated in this randomized, double-blind, parallel-group study initiated to compare the long-term therapeutic efficacy of twice daily levocabastine, a new topical H₁-receptor blocker, with that of sodium cromoglycate four times daily in the treatment of pollen-provoked conjunctivitis. There was no statistically significant difference in therapeutic efficacy between the two treatment groups, although a positive trend in favour of levocabastine was observed. Global evaluations of therapeutic efficacy were similar in both treatment groups. A total of 94% of levocabastine-treated patients rated treatment to be excellent or good compared with 86% of patients in the sodium cromoglycate group. Moreover, there were no significant differences in the severity of allergic symptoms reported on the patient diary cards. Patients were permitted to use rescue medication (oral terfenadine and betamethasone nasal spray) if symptoms became severe. The use of rescue medication was lower in the levocabastine group than in the sodium cromoglycate group. The mean number of days on which rescue medication was used was 12.8 and 26.9 in the two groups, respectively. The incidence, and type, of adverse reactions was similar in both patient groups. Levocabastine is well-tolerated and at least as effective as sodium cromoglycate in the treatment of pollen-provoked conjunctivitis.     

Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis

The efficacy, tolerability, and adverse-effect profile of the recently developed, topical antihistamine levocabastine were compared with those of sodium cromoglycate in a 4-week double-blind, placebo-controlled trial in 95 patients with seasonal allergic conjunctivitis. At the end of the trial, global therapeutic efficacy was considered to be excellent or good in 87% of levocabastine-treated patients, as compared with 68% of sodium cromoglycate-treated patients ( P = 0.006) and 63% of those who received placebo ( P = 0.05). After 4 weeks of treatment, levocabastine patients had experienced significantly greater relief from their most severe ocular symptom than patients in the sodium cromoglycate group ( P < 0.05). Furthermore, 37% of levocabastine-treated patients were virtually symptom-free for at least 75% of the treatment period, as compared with only 6% of patients in the sodium cromoglycate group ( P < 0.01) and 4% of those who received placebo ( P < 0.01). Moreover, this trend was maintained on days when the pollen count was high, when the corresponding figures were 33%, 6% ( P = 0.02), and 4% ( P = 0.02), respectively. Levocabastine was well tolerated. Indeed, the incidence of adverse reactions was no greater in the levocabastine group than in the placebo group. Topical levocabastine is an effective and well-tolerated drug for the prophylaxis and treatment of seasonal allergic conjunctivitis.     

Topical sodium cromoglycate (Opticrom®) relieves ongoing symptoms of allergic conjunctivitis within 2 minutes

Montan P, Zetterström O, Eliasson E, Strömquist L-H. Topical sodium cromoglycate (Opticrom®) relieves ongoing symptoms of allergic conjunctivitis within 2 minutes.
Twelve patients with seasonal allergic conjunctivitis caused by either birch or timothy grass pollen were challenged out of season in both eyes, with the relevant allergen. Itching, redness, swelling, and tearing were assessed on a 0–3 scale. When a positive reaction, i.e., at least 4 points, had occurred in both eyes, one drop of 2% sodium cromoglycate was administered to one eye and one drop of placebo to the other eye in each patient, in a double-blind, randomized fashion. Symptoms were then assessed after 2, 10, 30, and 60 min. Sodium cromoglycate was statistically better than placebo in reducing the symptoms at 2, 10, and 30 min after the treatment had been administered, showing that topical application of 2% sodium cromoglycate can quickly relieve ongoing symptoms of allergic inflammation in the eve.     

Treating severe eye allergy

Allergic eye conditions, particularly seasonal allergic conjunctivitis (SAC), are common. Itching, oedema and hyperaemia are relieved with topical H₁-antagonists or sodium cromoglycate. The newer mast-cell stabilizing agent nedocromil sodium has a similar safety profile to sodium cromoglycate, but is more potent and has a more convenient twice-daily dosing regimen. When several placebo-controlled studies of its use in the treatment of SAC were analysed, it was found that 80% of patients reported symptom relief. In a further study, nedocromil sodium eyedrops (twice-daily dosing) had similar overall efficacy to sodium cromoglycate eyedrops (four-times-daily dosing) in subjects with SAC during the birch season, but during the period of highest pollen challenge, only the former agent was significantly more effective than placebo. Another study found that nedocromil sodium had efficacy equivalent to levocabastine over 7 days, but tended to have a more rapid onset of action. In patients with perennial allergic conjunctivitis (PAC) unresponsive to sodium cromoglycate, both clinicians and patients reported significantly better control of symptoms with nedocromil sodium eyedrops than with placebo. Recently, in a long-term study of treatment for vernal keratoconjunctivitis (VKC), it was found that nedocromil sodium 2% eyedrops produced a more rapid and marked improvement in symptoms than sodium cromoglycate 2% eyedrops and enabled lower use of steroid rescue medication. Both drugs were well tolerated and without serious side-effects.     

Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray

Fluticasone propionate aqueous spray, a new intranasal corticosteroid preparation, and disodium eromoglyeate 2% aqueous nasal spray, an established preventive treatment for seasonal allergic rhinitis, were compared in a double-blind, double-dummy, parallel-group, multicentric study in France. A total of 218 patients with seasonal allergic rhinitis caused by grass pollen (verified by positive skin prick test) were preventively treated before the onset of the grass pollen season with either fluticasone propionate 200 μg once daily or disodium cromoglycate 5.2 mg four times daily. Half of these doses was given in each nostril. Treatment started before the onset of the pollen season in most patients (178/218). Diary cards, including symptoms of rhinitis and usage of nasal sprays, were filled in twice daily for 5 weeks.
Terfenadine in 60-mg tablets and eye-drops could be used as rescue medications. We treated 110 patients with fluticasone propionate and 108 patients with disodium cromoglycate. Patients treated with flutieasone propionate had significantly more days free of primary efficacy symptoms of sneezing ( P < 0.001) and nasal discharge during the day ( P = 0.002), as well as free of all the other nasal symptoms ( P < 0.0l), and significantly lower median scores ( P < 0.05) for all nasal symptoms except nasal discharge than patients treated with disodium cromoglycate. There was no difference in eye symptoms or in rescue medication use between the two groups. Compliance with the treatment was assessed. Eleven patients recorded incorrect use of both nasal sprays for over 25% of days, and 55 patients recorded incorrect use of four-times-daily spray only; no patient recorded incorrect use of morning spray only. Both treatments were generally well tolerated.     

A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma

We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.     

Intra-nasal beclomethasone dipropionate and intra-nasal sodium cromoglycate: a comparative trial

Ten patients with either seasonal allergic or perennial rhinitis were treated with intra-nasal beclomethasone dipropionate B.P. (Beconase) and nine comparable patients were treated with sodium cromoglycate B.P. (Rynacrom). The beclomethasone dipropionate was administered as 50 μg per puff into each nostril three times a day and the sodium cromoglycate as one capsule insufflated into each nostril four times a day. Treatments were allocated on a randomized basis and each patient received a course of treatment lasting 2 weeks during the summer of 1973 when the pollen counts were high. Utilizing patient daily symptom diary cards, physician's assessment and by examination of the nasal mucosa prior to and at the end of treatment, it was concluded that both intra-nasal beclomethasone dipropionate and intra-nasal sodium cromoglycate effect a reduction in the symptoms associated with rhinitis. No side effects of importance were noted, nor were there any adverse changes observed in the state of the nasal mucosa.     

Double-blind trial of pentigetide ophthalmic solution, 0.5%, compared with cromolyn sodium, 4%, ophthalmic solution for allergic conjunctivitis

Fifty patients (25 per group) with the signs and symptoms of allergic conjunctivitis confirmed by positive skin test enrolled in this randomized, double-blind, parallel group, 2-week comparison of pentigetide, 0.5%, ophthalmic solution (Pentyde) and cromolyn sodium, 4%, USP ophthalmic solution (Opticrom). The physician and the patient rated the patient's overall ocular condition on days 3, 8, and 15. On day 15 both the physician and the patients rated the pentigetide group as significantly (Chi-square, P less than .05) more improved than the cromolyn sodium group. The physician rated independently conjunctival symptoms and ocular signs at days 1, 3, 8, and 15. Improvement in signs and symptoms favored pentigetide in the majority of comparisons to cromolyn sodium (14 of 18). The pentigetide group showed significantly (ANOVA, P less than .05) greater improvement in hyperemia, edema, lacrimation, and blurred vision/photophobia. Patients completed daily diaries for seven symptoms. At the end of the study, comparisons to baseline between groups favored the pentigetide group for six of the seven symptoms; for itching, improvement favored significantly (ANOVA, P less than .05) the pentigetide group. The mean severity of all symptoms decreased by 64% in the pentigetide group as compared with a decrease of 46% in the cromolyn sodium group. Adverse experiences were minor and comparable in both groups. No clinically abnormal changes were noted for visual acuity, intraocular pressure, or common laboratory tests. This double-blind, active-controlled trial demonstrates that pentigetide, 0.5%, ophthalmic solution is safe and effective in the treatment of allergic conjunctivitis.     

Efficacy, cost-effectiveness, and tolerability of mometasone furoate, levocabastine, and disodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis.

BACKGROUND: Current guidelines recommend intranasal glucocorticosteroids as first-line therapy for seasonal allergic rhinitis. OBJECTIVE: To compare the efficacy, cost-effectiveness, and tolerability of the topical glucocorticosteroid mometasone furoate, the topical antihistamine levocabastine hydrochloride, and the cromone disodium cromoglycate in seasonal allergic rhinitis. METHODS: This study was performed during the 2003 grass pollen season as an open, randomized, parallel-group, single-center study of 123 patients assigned to receive mometasone furoate (200 microg once daily), levocabastine hydrochloride (200 microg twice daily), or disodium cromoglycate (5.6 mg 4 times daily). Symptom scores and nasal inspiratory peak flow measurements were recorded in a patient diary. The global efficacy of the study medication was evaluated by patients after treatment. Eosinophil cationic protein concentrations were measured in nasal secretions before and after treatment. Cost-effectiveness was evaluated as medication cost per treatment success. RESULTS: Mometasone furoate therapy was significantly superior to the use of levocabastine or disodium cromoglycate with respect to all nasal symptoms, the global evaluation of efficacy, and eosinophil cationic protein concentration. Furthermore, mometasone furoate therapy was significantly superior to disodium cromoglycate therapy with respect to nasal inspiratory peak flow. Medication cost per treatment success was lowest with mometasone furoate use and highest with levocabastine use. CONCLUSION: This is the first study to compare mometasone furoate nasal spray with nonsteroidal topical treatments for seasonal allergic rhinitis. Mometasone furoate nasal spray was confirmed as a first-choice topical treatment option for seasonal allergic rhinitis.     

Cromolyn sodium in seasonal allergic conjunctivitis

A formulation of 2% cromolyn sodium (CS) ophthalmic solution without the preservative, 2-phenylethanol, was compared with placebo in 58 patients with seasonal allergic conjunctivitis. Selection was based on history and positive skin tests. Neither immunotherapy nor use of antihistamines was allowed. This study was double-blinded and stratified by RAST scores to assure comparable groups. Either CS or placebo was used six times daily. Patients were observed weekly for 5 weeks during the peak of the fall weed-pollen exposure. Nasal symptoms were treated as required with beclomethasone nasal spray, and uncontrolled ocular symptoms were treated with boric acid and ephedrine solution. Nasal and ocular symptoms were recorded. There was a significant suppression of eye symptoms in the group receiving CS ophthalmic solution (p less than 0.02) during weeks 2, 4, and 5. There was a trend for nasal symptoms and the requirement for nasal beclomethasone to be less in patients receiving CS.     

Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis

This multicenter, double-blind, double-dummy, parallel-group trial was initiated to compare the efficacy and tolerability of two antihistamines, topical levocabastine (eye-drops and nasal spray) and oral loratadine, for the treatment of seasonal allergic rhinoconjunctivitis in the primary care setting. A total of 95 adult patients participated in the study with a treatment duration of 5 weeks. Forty-seven patients were randomized to receive twice daily levocabastine eye-drops and nasal spray plus an oral placebo, and 48 to receive once daily oral loratadine with placebo eye-drops and nasal spray. Naphazoline eye-drops and xylometazoline nasal spray were permitted as rescue medication. No statistically significant intergroup differences in therapeutic efficacy were observed. Symptom severity was comparable in the two treatment groups throughout the trial period. At the end of the study, 86% of levocabastine-treated patients considered global therapeutic efficacy to be excellent or good, as compared with 77% of those who received loratadine. This difference was not statistically significant. There were no significant differences in the use of rescue medication or in the incidence or severity of adverse events in the two treatment groups. In conclusion, levocabastine eye-drops and nasal spray appear to be as effective and well tolerated as oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis.     

A comparative trial of flunisolide and sodium cromoglycate nasal sprays in the treatment of seasonal allergic rhinitis

A trial of flunisolide nasal spray and sodium cromoglycate nasal spray in the treatment of hay fever was carried out during the summer of 1978. Sixty-seven patients all suffering from grass-pollen hay fever were given either flunisolide or sodium cromoglycate nasal sprays for 7 weeks. Patients were seen at 0,3 and 7 weeks and they also kept a daily record of symptoms. Overall assessment of symptom control and the patients daily records of sneezing showed flunisolide to be significantly superior to sodium cromoglycate. Patients records of symptoms correlated well with daily pollen counts. Side-effects were similar in both treatment groups and consisted mainly of mild naso-pharyngeal irritations.     

Double-blind group comparative trial of sodium cromoglycate eye ointment and placebo in the treatment of allergic eye diseases

Thirty-one patients with allergic eye diseases were treated three times daily for 4 weeks in a double-blind trial comparing sodium cromoglycate eye ointment with placebo. Patients' and clinician's assessment of symptoms and overall opinions of treatment showed sodium cromoglycate was significantly better than placebo and was well tolerated.     

Sodium cromoglycate as a replacement for inhaled corticosteroids in mild-to-moderate childhood asthma

We investigated whether sodium cromoglycate 10 mg three times daily, delivered as an aerosol via Nebuhaler (in addition to terbutaline 0.5 mg three times daily), could replace inhaled steroid in children with mild-to-moderate asthma. Children (mean age 10.3 years) were randomly allocated to 12-week treatment with sodium cromoglycate 10 mg plus terbutaline 0.5 mg (group A; n =30) or placebo plus terbutaline 0.5 mg (group B; n =32), both taken three times a day. The daily steroid dose was reduced by 50 μg/ week for 4 weeks from a starting dose of 200 μg. Fewer patients withdrew owing to worsening asthma from group A ( n =1) than group B ( n =11). Symptom scores, morning and evening peak flows, and additional β₂-agonist usage, recorded on diary cards, were better in group A than group B. Lung function measured at clinic visits was unchanged in either group. Overall opinions of efficacy favoured Group A. Adverse events were similar in the groups. Sodium cromoglycate plus terbutaline substituted effectively for inhaled steroid therapy.     

A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract

Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P<0.05 to P<0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P<0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe.