Dysmenorrhea
Conditions
Keywords
Sildenafil
Brief summary
The primary hypothesis is that a 100mg single dose of sildenafil citrate (Viagra) will have a higher improvement rate when compared to placebo in the treatment of moderate to severe primary dysmenorrhea.
Detailed description
It is well established that excess prostaglandin production in primary dysmenorrhea leads to ischemia of the uterine muscle, which consequently causes pelvic pain. A large number of drugs have been studied for pain relief in dysmenorrhea patients, with non-steroid anti-inflammatory drugs (NSAIDS) being the most effective with the overall success rate of more than 75%. Sildenafil citrate (Viagra) is an inhibitor that augments the vasodilatory effects of nitric oxide by preventing the degradation of Cyclic guanosine monophosphate (cGMP) in the uterine muscle. Sildenafil is commonly used in the treatment of male erectile dysfunction, pulmonary hypertension in children and adults, and in vitro fertilization. To date it has not been used in the treatment of primary dysmenorrhea.
Interventions
DRUGSildenafil Citrate
A single vaginal dose of sildenafil citrate 100 mg and monitored for 4 hours.
DRUGPlacebo
A single vaginal dose of placebo and monitored for 4 hours.
Sponsors
National Institutes of Health (NIH)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Primary dysmenorrhea at current visit, with a visual analogue scale (VAS) score of \>35; pain defined as moderate or severe on a categorical of none, mild, moderate, severe.
Exclusion criteria
* Secondary dysmenorrhea * Any current medication * Serious medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Was Total Pain Relief Over 4 Hours (TOPAR4), Comparing a Single Dose of Sildenafil 100 mg to a Single Dose of Placebo. | Hours 1, 2, 3 and 4. | The Total Pain Relief (TOPAR) Scale rates the level of pain relief on a scale of 0=None, 1=Mild, 2=Moderate, 3=Excellent, 4=Complete. The TOPAR scale was completed each hour after administration of study drug for a total of 4 hours. The 4 hourly scores were summed for a final TOPAR4 score that ranged between 0 and 16, with higher values indicating greater pain relief over time. Missing TOPAR scores after the first hour were imputed using the last-observation-carried-forward approach. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Each hour of the study (0, 1, 2, 3, 4). | The Visual Analog Scale (VAS) assesses pain intensity. The scale is 100 mm long; the extremes of the scale are to the left, no pain and to the right, worst pain I have ever felt. The VAS score is determined by measuring the distance (in mm) from the left side of the scale to the point that the patient marked. The score ranges from 0 to 100, with higher values indicating greater pain. |
Countries
Croatia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Citrate A single vaginal dose of sildenafil citrate 100 mg. | 13 |
| Placebo A single vaginal dose of placebo. | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Sildenafil Citrate | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 23.7 years STANDARD_DEVIATION 5.7 | 23.5 years STANDARD_DEVIATION 5.2 | 23.3 years STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 25 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 25 Participants | 12 Participants |
| Region of Enrollment Croatia | 13 participants | 25 participants | 12 participants |
| Sex: Female, Male Female | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
The Primary Outcome Was Total Pain Relief Over 4 Hours (TOPAR4), Comparing a Single Dose of Sildenafil 100 mg to a Single Dose of Placebo.
The Total Pain Relief (TOPAR) Scale rates the level of pain relief on a scale of 0=None, 1=Mild, 2=Moderate, 3=Excellent, 4=Complete. The TOPAR scale was completed each hour after administration of study drug for a total of 4 hours. The 4 hourly scores were summed for a final TOPAR4 score that ranged between 0 and 16, with higher values indicating greater pain relief over time. Missing TOPAR scores after the first hour were imputed using the last-observation-carried-forward approach.
Time frame: Hours 1, 2, 3 and 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sildenafil Citrate | The Primary Outcome Was Total Pain Relief Over 4 Hours (TOPAR4), Comparing a Single Dose of Sildenafil 100 mg to a Single Dose of Placebo. | 11.9 units on a scale | Standard Deviation 3.2 |
| Placebo | The Primary Outcome Was Total Pain Relief Over 4 Hours (TOPAR4), Comparing a Single Dose of Sildenafil 100 mg to a Single Dose of Placebo. | 6.4 units on a scale | Standard Deviation 2.1 |
Comparison: With 26 subjects per treatment group and an assumed within-group standard deviation of 7 units, the study was designed to have 90% statistical power for a two-sided, 0.05 significance level test to detect a difference of 6.5 units in TOPAR4 between a single dose of 100 mg of sildenafil and placebo. However, we anticipated subject drop-out as high as 15%; therefore, we planned to recruit 31 subjects per treatment group.p-value: <0.00195% CI: [2.9, 7.6]ANCOVA
Secondary
Improvement in Pain Severity Determined by Visual Analog Scale (VAS).
The Visual Analog Scale (VAS) assesses pain intensity. The scale is 100 mm long; the extremes of the scale are to the left, no pain and to the right, worst pain I have ever felt. The VAS score is determined by measuring the distance (in mm) from the left side of the scale to the point that the patient marked. The score ranges from 0 to 100, with higher values indicating greater pain.
Time frame: Each hour of the study (0, 1, 2, 3, 4).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil Citrate | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 0 | 91.2 mm | Standard Deviation 11.2 |
| Sildenafil Citrate | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 3 | 13.8 mm | Standard Deviation 25.3 |
| Sildenafil Citrate | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 1 | 65.2 mm | Standard Deviation 21.2 |
| Sildenafil Citrate | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 4 | 8.8 mm | Standard Deviation 25 |
| Sildenafil Citrate | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 2 | 23.4 mm | Standard Deviation 25.3 |
| Placebo | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 4 | 51.4 mm | Standard Deviation 26.6 |
| Placebo | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 2 | 72.5 mm | Standard Deviation 11.8 |
| Placebo | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 0 | 95.6 mm | Standard Deviation 5.3 |
| Placebo | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 1 | 88.6 mm | Standard Deviation 10.9 |
| Placebo | Improvement in Pain Severity Determined by Visual Analog Scale (VAS). | Hour 3 | 58.5 mm | Standard Deviation 19.8 |
p-value: <0.00195% CI: [-58.3, -26.8]Mixed Models Analysis