The team, from the United States, sought to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures.
They conducted a randomized, double-blind study of intra-anally applied nitroglycerin ointment in 304 patients with chronic anal fissures.
The patients were randomly assigned to 1 of 8 treatment regimens (0.0, 0.1, 0.2, or 0.4% nitroglycerin ointment applied 2 or 3 times per day), for up to 8 weeks.
A dose-measuring device was used to standardize the delivery of the ointment.
The healing of fissures was assessed by physical examination using an observer who was unaware of treatment allocations.
Patients assessed the pain intensity daily by completing a diary containing a visual analog scale. Average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation were all assessed.
|21% pain reduction with 0.4% nitroglycerin.
| Diseases of the Colon and Rectum |
The team found that there were no significant differences in fissure healing among any of the treatment groups.
All groups, including the placebo, had a healing rate of approximately 50%.
This rate of placebo response was inexplicably higher than previously reported in the literature.
However, they found that treatment with 0.4% nitroglycerin ointment was associated with a significant decrease in average pain intensity.
The decreases in pain were observed by day 4 of the treatment.
After 8 weeks of treatment, the difference between the 0.4% nitroglycerin group and the control group, was a 21% reduction in average pain.
On the whole, treatment was well tolerated, with only 3% of patients discontinuing treatment because of headaches.
Headaches were the primary adverse event and were dose related.
Dr Randolph Bailey's team concluded, "Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures".