Hemorrhoids, Pregnancy
Conditions
Keywords
Hemorrhoids, Pregnancy, antihemorrhoidal, Proctofoam, infants
Brief summary
The purpose of this study is to evaluate the fetal safety of topical application of Proctofoam-HC®, an antihemorrhoidal, in the third trimester of pregnancy.
Detailed description
Hemorrhoids are a frequent condition in pregnancy. The rate is increased as pregnancy progresses, and they affect up to 24% of pregnant women in the third trimester. Complications of untreated hemorrhoids include bleeding, prolapse, soiling, discharge with perianal irritation and itching, and in severe cases, severe pain and venous engorgement which could even lead to thrombosis and infarction. Hemorrhoids are treated with a variety of suppositories and gels, based on analgesic and anti-inflammatory effects. The safety of these antihemorrhoidal products has not yet been documented in pregnant women. Proctofoam-HC® has been on the Canadian market for 25 years. It combines the anti-inflammatory action of hydrocortisone with the surface anesthetic effect of pramoxine HCl. It is approved for temporary relief of anorectal inflammation, pruritus, pain and swelling associated with haemorrhoids, fissures, pruritus ani, cryptitis, proctitis and postoperative pain. We hypothesize that local application of Proctofoam-HC® in the third trimester of pregnancy is safe for the mother and fetus.
Interventions
DRUGProctofoam-HC®
Observational study of the exposure to Proctofoam-HC®
Sponsors
Duchesnay Inc.
The Hospital for Sick Children
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For intervention group, any pregnant woman with a primary anorectal condition during the third trimester of pregnancy * For control group, women in third trimester of pregnancy not treated with Proctofoam, and matched on maternal age and smoking status * for either group,no other pregnancy complications
Exclusion criteria
* exposure to known teratogens during pregnancy as evident either during the prenatal or postnatal interview * insufficient English language skills to understand the questionnaires and assessment material * Women who have received other corticosteroid medications (systemic or topical)during pregnancy * Women with the following conditions: abscess, fistula, tuberculosis, varicella, acute Herpes Simplex or fungal infection * age less than 18 years * History of previous reaction to any of the product's components, such as: local irritation, hypertrichosis, hypopigmentation, etc. * Known Intrauterine Growth Restriction (IUGR) or a chronic state that may cause IUGR (SLE, placental insufficiency). * Multi fetal pregnancy * Binge alcohol consumption (5 or more drinks on one occasion,in a row or within a short period of time)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Birth-weight | until delivery | Weight of the baby measured in grams at time of birth. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mode of Delivery | at birth | Method of delivery for both groups: vaginal or caesarean section |
| Prematurity | at birth | birth at \<37 gestational weeks |
| Gestational Age at Delivery | until delivery | Fetal gestational age at delivery |
| Low Birth Weight at Birth | at birth | Low birth weight (birth weights \<2500 grams) |
| Neonatal Health | at birth | Neonatal health at birthyes=need for medical attention or intervention after birth, abnormalities detected, no= no need for medical attention, no abnormalities detected at birth |
| Fetal Distress | at birth | Presence of fetal distress at birth: heart deceleration/acceleration, meconium/amniotic fluid |
Countries
Canada
Participant flow
Recruitment details
In this multicentre study we recruited pregnant women who were prescribed Proctofoam-HC for hemorrhoids by their physicians and who completed two telephone interviews using two specially designed questionnaires.
Pre-assignment details
There were no significant events that occur before assignment of the enrolled patients to groups.
Participants by arm
| Arm | Count |
|---|---|
| Proctofoam-HC® Proctofoam-HC® aerosol foam canister for 36 applications. One applicatorful should be injected into the anus (or perianal area) two or three times daily and after bowel evacuation. | 204 |
| Control Control, who were not exposed to any teratogens during the course of the pregnancy and to Proctofoam-HC, any of its components, or any other topical corticosteroids or local anaesthetics during the course of their pregnancy. | 204 |
| Total | 408 |
Baseline characteristics
| Characteristic | Control | Proctofoam-HC® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 204 Participants | 204 Participants | 408 Participants |
| Age, Continuous | 31.5 years STANDARD_DEVIATION 4.9 | 32 years STANDARD_DEVIATION 4.9 | 31.75 years STANDARD_DEVIATION 4.9 |
| Region of Enrollment Canada | 204 participants | 204 participants | 408 participants |
| Sex: Female, Male Female | 204 Participants | 204 Participants | 408 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 / 204 | 0 / 204 |
| serious Total, serious adverse events | 0 / 204 | 0 / 204 |
Outcome results
Primary
Birth-weight
Weight of the baby measured in grams at time of birth.
Time frame: until delivery
Population: Estimated number of 200 patients per arm, to detect significant difference of 200g in birth weight at a power of 80% and alpha of 5%. Seven pairs of twin pregnancies were excluded from the comparison of birth weight.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proctofoam-HC® | Birth-weight | 3406.9 grams | Standard Deviation 452.7 |
| Control | Birth-weight | 3487.7 grams | Standard Deviation 491.4 |
Comparison: Null hypothesis: Birth weight in pregnancies exposed to Proctofoam-HC will be the same as control pregnancies.~To detect a clinically significant decrease of 200 g in birth weight at a power of 80% and alpha of 5%, 200 women per group were required. Post hoc power analysis of our cohort revealed that, in fact, we had a 91.5% power to detect a 200 g difference in birth weight between the two groups.p-value: 0.1795% CI: [0, 200]t-test, 2 sided
Secondary
Fetal Distress
Presence of fetal distress at birth: heart deceleration/acceleration, meconium/amniotic fluid
Time frame: at birth
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Fetal Distress | Fetal distress | 36 participants |
| Proctofoam-HC® | Fetal Distress | No fetal distress | 163 participants |
| Control | Fetal Distress | Fetal distress | 31 participants |
| Control | Fetal Distress | No fetal distress | 142 participants |
Comparison: Fetal Distress The null hypothesis is that the proportion of fetal distress in the Proctofoam and Control groups will be the same.p-value: 0.97McNemar
Secondary
Gestational Age at Delivery
Fetal gestational age at delivery
Time frame: until delivery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proctofoam-HC® | Gestational Age at Delivery | 39.4 gestational weeks | Standard Deviation 1.4 |
| Control | Gestational Age at Delivery | 39.1 gestational weeks | Standard Deviation 2.5 |
p-value: 0.1695% CI: [0, 3]Wilcoxon (Mann-Whitney)
Secondary
Low Birth Weight at Birth
Low birth weight (birth weights \<2500 grams)
Time frame: at birth
Population: Per protocol, the estimated number of 200 patients per arm, to detect significant difference of 200g in birth weight (primary outcome) for a power of 80% and alpha of 5% was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Low Birth Weight at Birth | Yes | 6 participants |
| Proctofoam-HC® | Low Birth Weight at Birth | No | 194 participants |
| Control | Low Birth Weight at Birth | Yes | 3 participants |
| Control | Low Birth Weight at Birth | No | 198 participants |
Comparison: Low birth weight \<2,500g; The null hypothesis is that the proportion of low birth weight babies in the Proctofoam and Control groups will be the same.p-value: 0.31McNemar
Secondary
Mode of Delivery
Method of delivery for both groups: vaginal or caesarean section
Time frame: at birth
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Mode of Delivery | Vaginal delivery | 173 participants |
| Proctofoam-HC® | Mode of Delivery | Caesarean section | 31 participants |
| Proctofoam-HC® | Mode of Delivery | Unknown | 0 participants |
| Control | Mode of Delivery | Vaginal delivery | 146 participants |
| Control | Mode of Delivery | Caesarean section | 55 participants |
| Control | Mode of Delivery | Unknown | 3 participants |
Comparison: The null hypothesis is that the proportion of vaginal deliveries in the Proctofoam and Control groups will be the same (ie. there will not be a greater proportion of complicated deliveries in either group).p-value: 0.003McNemar
Secondary
Neonatal Health
Neonatal health at birthyes=need for medical attention or intervention after birth, abnormalities detected, no= no need for medical attention, no abnormalities detected at birth
Time frame: at birth
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Neonatal Health | Yes (present neonatal health concerns) | 28 participants |
| Proctofoam-HC® | Neonatal Health | No (absent neonatal health concerns) | 171 participants |
| Control | Neonatal Health | Yes (present neonatal health concerns) | 24 participants |
| Control | Neonatal Health | No (absent neonatal health concerns) | 154 participants |
Comparison: The null hypothesis is that the proportion of healthy babies (not requiring NICU (neonatal intensive care unit) or additional medical monitoring) will be the same between the Proctofoam and Control groups.p-value: 0.87McNemar
Secondary
Prematurity
birth at \<37 gestational weeks
Time frame: at birth
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Prematurity | yes | 8 participants |
| Proctofoam-HC® | Prematurity | no | 193 participants |
| Control | Prematurity | yes | 10 participants |
| Control | Prematurity | no | 180 participants |
Comparison: The null hypothesis is that the proportion of pre-term births in the Proctofoam and Control groups will be the same.p-value: 0.55McNemar
Post Hoc
Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth
Assessment of neonate's morphology and function of cardiovascular system in the first two weeks after birth
Time frame: neonatal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Cardiovascular anomalies | 2 participants |
| Proctofoam-HC® | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Heart murmur | 6 participants |
| Proctofoam-HC® | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Premature atrial contraction | 0 participants |
| Control | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Cardiovascular anomalies | 0 participants |
| Control | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Heart murmur | 4 participants |
| Control | Cardiovascular Neonatal Health Concerns in the First Two Weeks After Birth | Premature atrial contraction | 2 participants |
p-value: 0.99Fisher Exact
Post Hoc
Neonatal Health Concerns-infections
Infections occuring in the neonatal period
Time frame: neonatal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Neonatal Health Concerns-infections | Urinary tract infections | 2 participants |
| Proctofoam-HC® | Neonatal Health Concerns-infections | Streptococcus B infection | 0 participants |
| Proctofoam-HC® | Neonatal Health Concerns-infections | Pneumonia | 0 participants |
| Proctofoam-HC® | Neonatal Health Concerns-infections | Leucocytosis | 2 participants |
| Control | Neonatal Health Concerns-infections | Leucocytosis | 0 participants |
| Control | Neonatal Health Concerns-infections | Urinary tract infections | 0 participants |
| Control | Neonatal Health Concerns-infections | Pneumonia | 2 participants |
| Control | Neonatal Health Concerns-infections | Streptococcus B infection | 2 participants |
p-value: 0.99Fisher Exact
Post Hoc
Other Neonatal Health Concerns
Time frame: neonatal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Other Neonatal Health Concerns | Colic | 0 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Poor feeding | 2 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Conjuctivitis | 4 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Poor weight gain | 2 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Milk allergy | 0 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Anemia | 0 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Myopia | 0 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Renal calculi | 0 participants |
| Proctofoam-HC® | Other Neonatal Health Concerns | Hypoglycemia | 4 participants |
| Control | Other Neonatal Health Concerns | Renal calculi | 2 participants |
| Control | Other Neonatal Health Concerns | Colic | 4 participants |
| Control | Other Neonatal Health Concerns | Milk allergy | 2 participants |
| Control | Other Neonatal Health Concerns | Conjuctivitis | 0 participants |
| Control | Other Neonatal Health Concerns | Hypoglycemia | 0 participants |
| Control | Other Neonatal Health Concerns | Poor feeding | 0 participants |
| Control | Other Neonatal Health Concerns | Poor weight gain | 2 participants |
| Control | Other Neonatal Health Concerns | Anemia | 2 participants |
| Control | Other Neonatal Health Concerns | Myopia | 2 participants |
Post Hoc
Respiratory Neonatal Health Concerns
Time frame: neonatal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Respiratory Neonatal Health Concerns | Pulmonary aspiration | 4 participants |
| Proctofoam-HC® | Respiratory Neonatal Health Concerns | Mild asthma | 2 participants |
| Proctofoam-HC® | Respiratory Neonatal Health Concerns | Tachypnea | 0 participants |
| Control | Respiratory Neonatal Health Concerns | Pulmonary aspiration | 0 participants |
| Control | Respiratory Neonatal Health Concerns | Mild asthma | 2 participants |
| Control | Respiratory Neonatal Health Concerns | Tachypnea | 2 participants |
p-value: 0.99Fisher Exact
Post Hoc
Skin Conditions in Neonatal Period
Time frame: neonatal period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proctofoam-HC® | Skin Conditions in Neonatal Period | Rash | 2 participants |
| Proctofoam-HC® | Skin Conditions in Neonatal Period | Eczema | 0 participants |
| Proctofoam-HC® | Skin Conditions in Neonatal Period | Acne | 0 participants |
| Control | Skin Conditions in Neonatal Period | Rash | 2 participants |
| Control | Skin Conditions in Neonatal Period | Eczema | 2 participants |
| Control | Skin Conditions in Neonatal Period | Acne | 2 participants |
p-value: 0.35Fisher Exact