Thank you for joining the EAGeR study. During the study you will be coming into the clinic for regular study visits. You will also have regular phone contact with study staff. Your cooperation and compliance with the study protocol is very important to us.
If you have any problems don't hesitate to contact your study center: University at Buffalo 1-716-829-3128
University of Utah 1-866-912-1967
The Commonwealth Medical College (Scranton, PA) 1-570-207-1058
Study follow-up
The study treatment is:
A daily pill of low-dose aspirin or placebo and
A daily pill of folic acid.
Follow-up will continue for:
Up to six menstrual cycles while trying to conceive or,
If you become pregnant throughout pregnancy.
Active Follow-up
(Your first two menstrual cycles while participating in the study)
During the first two cycles of follow-up we ask that you complete a number of daily tasks which includes taking your study pills and folic acid:
Fill out the daily diary by answering a few simple questions,
Collect and store first morning urine,
Use the fertility monitor
During this time, you will be asked to visit the study clinic about every two weeks. Scheduling of study visits is based on the information obtained from the fertility monitor as well as the timing of your menses (periods). Study staff will do their best to accommodate any special needs you may have.
Passive Follow-up
(The four menstrual cycles following Active Follow-up)
The next four cycles of follow-up include monthly clinic visits with a short phone contact in between visits. In these four months you will continue to use the fertility monitor. During passive follow-up and throughout the course of the study you will continue to take your study pills and folic acid daily.
Pregnancy Follow-up
Whether you are in active or passive follow-up, when you have a positive pregnancy test you will then enter into pregnancy follow-up. Throughout your pregnancy, we will see you for a few scheduled clinic visits and have regular contact with you. During your pregnancy follow-up, through week 36, you will continue to take your study pills and folic acid daily.
During the first four weeks of Pregnancy Follow-up we ask that every day you:
o Fill out the pregnancy daily diary and
o Collect and store first morning urine.
Throughout the trial the safety of participants is closely monitored and all information collected is kept confidential and private.
Scheduling Study Visits
It is very important that your study visits occur during specific times of your menstrual cycle. The study staff will schedule your visits according to the information we have from you regarding your menstrual cycle as well as information from the fertility monitor tests. Please realize, however, that the scheduling is tentative and the visits will likely need to be changed as we learn more information about your menstrual cycle.
Randomization Visit:
The randomization visit will be your second visit in the study. This is the visit where you will you get your study pills, fertility monitor, daily diary, and home urine collection kit. This visit MUST take place between Day 2 to 4 of your period. The study visit we have scheduled for you is tentative. Please call the study clinic the first day your menstrual flow starts. You should also call the clinic if your menstrual flow has not started by the day before your scheduled visit. Study staff may need to change your visit so that it occurs during the day 2 to 4 window, by rescheduling the randomization visit to be earlier or later than originally scheduled. In case the visit cannot be re-scheduled within the allowable window, the visit will need to be moved to the next menstrual cycle.
First Two Menstrual Cycles in Active Follow-up:
During your first two menstrual cycles while in the study, it is important that your mid-cycle clinic visit occurs as close as possible to the “peak” fertility day according to the Clearblue fertility monitor. Please call the study clinic on the day your monitor first shows the “peak” fertility sign. We would like to schedule your mid-cycle visits within two days of the first peak day on your fertility monitor. If you reach the date of your regularly scheduled appointment and no “peak” fertility sign has appeared, you should still keep the appointment without any further rescheduling, even if the “peak” fertility sign appears later on, which it will in some cases.
Remaining Visits in Active and Passive Follow-up:
The rest of the study visits during Active and Passive Follow-up should occur on Day 2 to 4 of your menstrual cycles. The study visit dates we have scheduled for you in your last clinic visit are tentative. Please call the study clinic if your period starts more than 1 day before your scheduled appointment. If you reach the date of your regularly scheduled appointment and your menstrual flow has not started, you should still keep the appointment without any further rescheduling.
You are provided with a Clearblue® fertility monitor (Unipath Limited) to help you monitor your fertility level during your participation in the EAGeR trial. The monitors have been reset according to the study needs. Please follow the instructions carefully.
On the second day of your period, turn on the monitor.
Pressing the “m” button will tell the monitor that your period has started. Pressing the “m” button also sets the time for your testing window. The monitor will only allow you to test during that window period. The window period will be 6 hours long. It will be 3 hours before and 3 hours after the time you set the “m” button. Therefore it is very important that you only press the “m” button at the time of the morning that you want to test your first morning urine (around the time you typically wake up).
For example, if you press the button at 7 am, then your testing window will be set for 4 am to 10 am. When you press the button, a “1” will appear to indicate that it is the first day of your period. If you do not set the monitor on the first day of your period (you forgot or the time of day was not right for first morning urine testing, for example, if your period does not start until the afternoon), then continue to hold the “m” button until the appropriate day of your cycle appears. For example, if you forgot to set this on the first day of your period and then remembered on day 2, then press the “m” button until a “2” appears. Make sure the “m” button is set at a time when it is convenient for you to test your first morning urine. You must press the “m” button by day 2.
You will only press the “m” button once at the beginning of a menstrual cycle.
Do not leave the monitor in the bathroom for long periods of time. Steam from the bathtub or shower will damage it. Also, be careful to keep the monitor away from the sink and the toilet when you are performing a test. If you drop it in water, the monitor may malfunction and need to be replaced.
When and how to test
Turn on the monitor every morning before you urinate to see if you are instructed to perform a test. In general, you will test the first morning urine starting on day 2 until the end of your menstrual cycle (up to day 31). If your cycle is longer then 31 days you will not be asked for a test until your next cycle begins.
You will test your first morning urine. If you forget to test your first morning urine, you should still try to test that day during your window period.
Collect your urine in a clean dry cup and insert the absorbent end of the test stick in the urine for 15 seconds (if you are doing daily urine collection and storage you should use the urine you have leftover in the cup after pouring the correct amount into the collection tube ).
While keeping the test stick pointed downwards, remove the protective cap from the handle and put it on the wet end of the stick. Gently wipe off any excess urine on the outside of the test stick with a tissue.
Place the cut corner of the test stick facing downwards into the test stick slot in the fertility monitor (the end with the window) and then push the rest of the test stick down until it lies flat and clicks into place. When the test stick is positioned correctly, the test stick symbol will flash for five minutes while the monitor is reading it. The monitor might turn off during this time.
After the monitor has read the test stick, it will display a symbol prompting you to remove the stick. If the monitor has turned off automatically, turn the monitor back on before removing the stick. You should see the symbol to remove the stick at that point. Remove the test stick and throw it away (they cannot be reused). Your fertility status will then be displayed as low, high or peak indicating the likelihood of conception. Record the fertility status (1=low, 2=high, or 3=peak) in your daily diary each day.
PEAK – when the monitor looks like this
You should call the clinic that day to report that you have peaked on the monitor. During active follow-up you will be scheduled for a clinic visit as soon as possible.
If you have any questions regarding use of the monitor please call us. If you are enrolled at the University at Buffalo, please call 1-716-829-3128. If you are enrolled at the University of Utah, please call 1-866-912-1967. More detailed instructions can also be found at www.eagertrial.org in the participant’s page.
Women who participate in the EAGeR trial will receive two types of pills: Study Pills which are either low-dose aspirin (81mg) or placebo and a pill of folic acid (400µg). Treatment continues throughout active and passive follow-up and through week 36 of pregnancy. Every day, take one Study Pill and one folic acid pill. It is best to take the pills at the same time every day. You can use a pill box where the pills for one week can be organized by day. If you have any side effects that may be related to study medication please call your center.
Please bring ALL your bottles and unused pills to each study visit even if the bottles are empty. Do NOT throw away any bottles. If you are using a pill box, also bring the box to each study visit.
Aspirin/Placebo (Study Pills)
Store your Study Pills in a dry place at normal room temperature – Do not store in the bathroom.
Keep the medication away from children.
Use exactly as directed; do not increase dose or frequency. Take the medication at about the same time every day, preferably in the morning.
If you forget to take your medication one day, take it as soon as you remember as long as it is still within the same day (in other words before midnight that day).
May take with food or milk to minimize gastrointestinal upset.
Do not use if the medication has a strong vinegar-like odor.
Swallow the capsules whole - Do not crush or chew.
Do not use other prescription or nonprescription medications containing aspirin or other pain relievers without consulting your doctor and study personnel.
Be aware that many combination non-prescription drugs, such as cold and cough products and sleep aids, may contain aspirin or other pain relievers. Please be sure to read the list of active ingredients on any non-prescription drug product that you take and/or ask your doctor or pharmacist before taking any product.
You may experience nausea, vomiting, gastric discomfort (frequent mouth care, small frequent meals, sucking lozenges, or chewing gum may help); gastrointestinal bleeding and ulceration (can occur with or without pain); or discoloration of stool (pink/red or dark, tarry stools).
Stop taking the Study Pills and call your doctor and study personnel if the following reactions occur: ringing in ears; persistent stomach pain; severe, unresolved nausea or vomiting; breathing difficulty or shortness of breath; unusual bruising or bleeding (bleeding in the mouth, urine, stool); or skin rash. If you experience nausea or vomiting during pregnancy (or shortness of breath during late pregnancy), do NOT stop the Study Pills. These are common symptoms during pregnancy.
If the nausea and vomiting or the shortness of breath is severe during pregnancy, you should call your regular physician.
If your doctor tells you to stop taking your Study Pills, please inform the study staff.
In the event you cannot reach your doctor or the study staff and your symptoms persist, please call Poison Control at 1-800-222-1222. Your call will automatically be directed to your local Poison Control Center.
Minimize alcohol use as combined use with the Study Pills may increase the risk of stomach ulceration and bleeding.
There are several prescription and over the counter medications that should not be used or should be used cautiously with the Study Pills. For example blood thinners (such as warfarin), steroids, or methotrexate are taken by individuals also taking aspirin, negative side effects may occur. Please inform all your healthcare providers that you may be taking aspirin as part of the study. In case of drug interactions, any time a health provider starts you on a new prescription or recommends an over the counter medication, make sure you inform him or her that you may be taking aspirin as part of the study. If your healthcare provider recommends stopping your Study Pills, please inform the study staff.
Folic acid
Adverse effects are very rare but may include allergic reactions, difficulty breathing, mild flushing, rash, and itchy skin. Inform the study staff and your doctor if any of these adverse effects occur. Folic acid may cause urine to turn more intensely yellow.
