Optimal treatment duration of glyceryl trinitrate for chronic anal fissure: results of a prospective randomized multicenter trial.
BACKGROUND
Chronic anal fissure (CAF) is a painful condition that is unlikely to resolve with conventional conservative management. Previous studies have reported that topical treatment of CAF with glyceryl trinitrate (GTN) reduces pain and promotes healing, but optimal treatment duration is unknown.


METHODS
To assess the effect of different treatment durations on CAF, we designed a prospective randomized trial comparing 40 versus 80 days with twice daily topical 0.4% GTN treatment (Rectogesic, Prostrakan Group). Chronicity was defined by the presence of both morphological (fibrosis, skin tag, exposed sphincter, hypertrophied anal papilla) and time criteria (symptoms present for more than 2 months or pain of less duration but similar episodes in the past). A gravity score (1 = no visible sphincter; 2 = visible sphincter; 3 = visible sphincter and fibrosis) was used at baseline. Fissure healing, the primary endpoint of the study, maximum pain at defecation measured with VAS and maximum anal resting pressure were assessed at baseline and at 14, 28, 40 and 80 days. Data was gathered at the end of the assigned treatment.


RESULTS
Of 188 patients with chronic fissure, 96 were randomized to the 40-day group and 92 to the 80-day group. Patients were well matched for sex, age, VAS and fissure score. There were 34 (19%) patients who did not complete treatment, 18 (10%) because of side effects. Of 154 patients who completed treatment, 90 (58%) had their fissures healed and 105 (68%) were pain free. There was no difference in healing or symptoms between the 40- and the 80-day group. There was no predictor of fissure healing. A low fissure gravity score correlated with increased resolution of pain (P < 0.05) and improvement of VAS score (P < 0.05) on both univariate and multivariate analysis. A lower baseline resting pressure was associated with better pain resolution on univariate analysis (P < 0.01). VAS at defecation and fissure healing significantly improved until 40 days (P < 0.001), while the difference between 40 and 80 days was not significant.


CONCLUSIONS
We found no benefits in treating CAF with topical GTN for 80 days compared to 40 days. Fissure healing and VAS improvement continue until 6 weeks of treatment but are unlikely thereafter.
Gagliardi
G
G
Italian Society of ColoRectal Surgery (SICCR) Coloproctology Unit of Rome, Rome, Italy. gagliarg@yahoo.com
Pascariello
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A
Altomare
D F
DF
Arcanà
F
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Cafaro
D
D
La Torre
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F
De Nardi
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P
Basso
L
L
De Stefano
I
I
Greco
V J
VJ
Vasapollo
L
L
Amato
A
A
Pulvirenti D'Urso
A
A
Aiello
D
D
Bove
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A
D000287:Administration, Topical; D000328:Adult; D000704:Analysis of Variance; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005401:Fissure in Ano / Q000175:diagnosis / Q000188:drug therapy*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use*; D010147:Pain Measurement; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D005996:Nitroglycerin