Download oral antibiotic prophylaxis of early infection

URCC 10994P(M)
Southeast Cancer Control Consortium Consent Form
ORAL ANTIBIOTIC PROPHYLAXIS OF EARLY INFECTION
IN MULTIPLE MYELOMA
Research Study
You have the right to know about the procedures that are used in your participation in clinical research so as to
afford you an opportunity to make the decision whether or not to undergo the procedure after knowing the risks
and hazards involved. This disclosure is not meant to frighten or alarm you; it is simply an effort to make you
better informed so you may give or withhold your consent to participate in clinical research.
Purpose of the Study
You have been diagnosed with a form of cancer called multiple myeloma. It has been explained to you that one
of the side effects associated with chemotherapy (drug treatment) for multiple myeloma is an increased risk of
infection. Previous studies have shown that during the first two months of chemotherapy, the incidence of
infection is 2-3 times higher than during the overall disease course. One of the ways of possibly reducing the
number of infections is to have patients take an antibiotic every day for the first two months of chemotherapy.
This is called prophylactic (preventive) antibiotic treatment. The antibiotic is being used as a preventive
treatment, rather than to treat an existing infection.
This study will compare the use of two frequently prescribed antibiotics, trimethoprim-sulfamethoxazole (also
known as TMP-SMX, Septra or Bactrim) and ciprofloxacin (or Cipro) with no antibiotic treatment. The purposes
of the study are: 1) to determine if the use of preventive antibiotics will significantly reduce the number of
infections caused by bacteria or other organisms, including those resistant to antibiotics during the first two
months of chemotherapy for multiple myeloma; 2) to determine the relative effectiveness and toxicity of the two
antibiotics; 3) to evaluate whether protection against early infection improves patients' response to chemotherapy.
The total number of patients to be enrolled in this study is 210. The expected duration of treatment on this study
is 2 months. You will be followed one additional month while on chemotherapy.
Description of Procedures
If you agree to participate in this study, you will be assigned one of the following treatment plans:
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3)
1)
no preventive antibiotic
2)
trimethoprim-sulfamethoxazole (TMP-SMX) for two months
ciprofloxacin or ofloxacin for two months
Since it is not clear which of the study treatment plans would be better for you, the study treatment plan which is
to be offered to you will be based upon a method of selection called randomization. Randomization means that
your doctor will call a statistical office which will assign one of the study treatment plans to you and that your
chance of receiving any of the three treatments is the same. Randomization is similar to the flip of a coin.
If you are assigned TMP-SMX you will take one tablet by mouth every 12 hours (two times a day) for two
months. If you are allergic to sulfa drugs and are assigned to TMP-SMX (which contains sulfa), you will be
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given Trimethoprim. This drug does not contain sulfa.
If you are assigned ciprofloxacin you will take one tablet by mouth every 12 hours (two times a day) for two
months.
If you are assigned no preventive antibiotic you will receive no antibiotics unless you develop an infection.
You will know which of the three treatment plans you are assigned to.
If you are assigned to receive ciprofloxacin or ofloxacin, you must avoid taking medications containing
theophylline such as Marax®, Quibron®, Theo-Dur®, Aerolate, Theolair, Respbid®, Slo-bid, T-Phyl®, and
Uniphyl®, as the resulting toxicity may be fatal. You should also avoid taking antacids as well as the drug
sucralfate (Carafate®) as these may interfere with absorption of ciprofloxacin or ofloxacin from the stomach.
While on this study, you must return to see your doctor if you develop fever or any other signs of infection. If
you should develop an infection, your doctor will treat you in a manner appropriate for the situation. If you were
assigned one of the preventive antibiotics, you may continue on that antibiotic for the entire two months, even if
you require additional treatment for an infection or your chemotherapy is changed, delayed for any length of time
or discontinued. If you experience unacceptable side effects from the antibiotic, it will be discontinued and you
will be followed with no further preventive antibiotic.
Prior to enrollment, you will have a bone marrow biopsy if one has not been done within the past 30 days. You
will also have x-rays of your chest and bones, blood work and urine studies if these have not been done within the
past 10 days. After enrollment to this study, regardless of which treatment plan you are assigned, you will be
evaluated by your doctor once a month for three months. As part of this evaluation you will have a physical
exam, blood work, and a record of any side effects and infections. After the initial three months, your medical
records will be reviewed every six months for incidence of infections and your disease response to chemotherapy.
This follow-up will continue as long as your myeloma is responding to treatment.
Risks and Discomforts
The drugs used in this study may cause all, some or none of the side effects listed. In addition there is always the
risk of very uncommon, unforeseeable, unexpected, fatal or previously unknown side effects occurring. It is
possible you may develop an infection with an antibiotic-resistant organism.
Trimethoprim-sulfamethoxazole (TMP-SMX, Septra or Bactrim)
Trimethoprim-sulfamethoxazole may cause lowering of red blood cells (responsible for carrying oxygen) which
can lead to an increased risk of anemia causing unusual weakness or tiredness, lowering of white blood cells
(responsible for fighting infection) which can lead to an increased risk of infection, and lowering of platelets
(responsible for causing blood to clot) which can lead to an increased risk of easy bruising and bleeding. It can
cause hemolytic anemia (low red blood cell count caused by damage to the red blood cells) which can cause back,
leg or stomach pains, loss of appetite, pale skin, fever, unusual tiredness or weakness, difficulty sleeping, and
restlessness. It can cause skin rashes, itchy skin, blistering skin, increased sensitivity to sunlight (including
sunlamps and tanning beds). TMP-SMX can cause nausea, vomiting, diarrhea, inflammation of the liver,
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difficulty swallowing, sore tongue, sore mouth, sore throat or abdominal pain. It can cause inflammation of the
joints and pain in the muscles and joints. TMP-SMX can cause headache and dizziness. If a pregnant woman
takes TMP-SMX, it can cause birth defects in the unborn child. If the mother takes the drug when she is breastfeeding a baby, the drug is found in the breast milk. TMP-SMX can also affect the kidneys (abnormal kidney
function tests, damaged kidneys, crystals in the urine, blood in the urine, and pain on urination).
TMP-SMX has been reported to interfere with the actions of the drug warafin which is given to prolong bleeding
time (or thin the blood). If you are taking this drug your doctor will monitor your bleeding times carefully. If you
are taking a thiazide diuretic (such as to treat high blood pressure), your blood will be monitored for a decrease in
the number of platelets.
Trimethoprim (Proloprim®, Trimpex®)
Trimethoprim is an antibiotic that avoids the side effects associated with the sulfonamide part of TMP-SMX.
Occasionally, skin rashes, itching skin, nausea, and vomiting have been reported. Also rarely reported is a
decrease in the white blood cell count, red blood cell count, and platelet count.
Ciprofloxacin (Cipro) or Ofloxacin
10/31/97Ciprofloxacin/ofloxacin is an antibiotic given two times a day. Drugs which are similar to ciprofloxacin or
ofloxacin have caused convulsions (seizures), pressure in the head, personality change, tremors, restlessness,
lightheadedness, confusion, and hallucinations. Serious and fatal allergic reactions including rash, itching, and
difficulty breathing have been seen with ciprofloxacin. Some patients have also experienced ulcers and sores in
the lower intestines. Crystals in the urine have also been found, and you should drink plenty of water in order to
avoid this. Skin discoloration and moderate to severe reaction to sunlight have also been seen.
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Ciprofloxacin and ofloxacin have been known to interact with other drugs to cause more severe side effects.
These drugs should be avoided: antacids containing aluminum, magnesium or calcium, products containing iron
or zinc, theophylline, caffeine, cyclosporine, warfarin or probenecid.
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Ofloxacin has been known to interact with non-steroid anti-inflammatory drugs and these should be avoided.
Also, if you are a diabetic on insulin, careful monitoring of your blood glucose is recommended if you take
ofloxacin.
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Despite the precautions listed above, side effects have been rarely reported with ciprofloxacin. These have
included nausea, diarrhea, vomiting, stomach pain, and headache. Elevations in tests to evaluate liver and kidney
function have also been seen. Other side effects were seen less than 1% of the time.
Pregnancy/Birth Control:
Due to the unknown risks and potential harm to the unborn fetus, sexually active women of childbearing potential
must use a reliable method of birth control while participating in this study. Reliable methods of birth control are
considered to be: abstinence (not having sex), oral contraceptives, Intrauterine device (IUD), DepoProvera,
Norplant, tubal ligation or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous
relationship (same partner). An acceptable, although less reliable method involves the careful use of condoms
and spermicidal foam or gel and/or a cervical cap or sponge. We encourage you to discuss this issue further with
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your doctors if you have any questions.
Pregnant women are excluded from participation in this study. If a woman becomes pregnant, she will be
withdrawn from the study. If a man fathers a child, there may be potential risk to the unborn baby; therefore,
female sexual partners of men on treatment should use an adequate form of birth control. Since most methods of
birth control are not 100% reliable, if you are a sexually active woman of childbearing potential, a pregnancy test
(at least 10 days from your last normal menstrual period) is required.
Risks associated with the blood draw are infection or bruising at the puncture site.
If you are unable to follow your doctor's instructions; side effects become very severe; new scientific
developments occur that indicate the treatment is not in your best interest; or your doctor feels that treatment is
no longer in your best interest, the study treatment would be stopped. Further treatment would then be discussed.
Benefits
A possible benefit of participating in this study is fewer infections if you are assigned treatment with a preventive
antibiotic, although this cannot be guaranteed.
Costs
You or your insurance carrier will be responsible for the costs of study medications, clinic visits, any hospital
admissions, laboratory tests, x-rays, and any other tests. How much you will have to pay depends on whether or
not you have insurance and what costs your insurance will cover. Insurance coverage cannot be guaranteed for
all tests and treatments related to this study.
You will be provided no financial compensation for participating in this research study. Any procedure related
solely to research which would not otherwise be necessary will be explained. Some of these procedures may
result in added costs and some of these costs may not be covered by your insurance. For example, the cost of
medicines to control side effects could result in added costs. In some cases, third party carriers (insurance
companies, health plans, Medicare or Medicaid) may not cover these costs. Any care required to treat side effects
(whether expected or unexpected) will be charged to you or your insurance company as in the case of standard
chemotherapy. Your doctor will discuss these with you and your participation is voluntary.
Alternatives
Alternative treatments which may be available to you include receiving either of the antibiotics as preventive
antibiotic without participating in this study, although it has not been determined that preventive treatment is
better. Another alternative is no preventive treatment.
Confidentiality
Confidentiality of information concerning you will be maintained. Your name, or identifying material will not be
released without your written permission, except as such release is required by law. A record of your progress
will be kept in confidential form at ________________________________________________ Hospital, and
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also in a computer file at the statistical headquarters of the University of Rochester Cancer Center (URCC).
There is a possibility that your medical records, blood samples, x-rays, scans, and pathology slides (including
identifying information) may be inspected and/or photocopied by authorized representatives of the National
Cancer Institute (NCI), the Food and Drug Administration (FDA), the Office of Protection from Research Risks
(OPRR), the Southeast Cancer Control Consortium, Inc. (SCCC), the Institutional Review Board (IRB) at your
hospital, the University of Rochester Cancer Center (URCC) or other federal or state government agencies in the
ordinary course of carrying out their governmental functions. A qualified representative of the manufacturer of
the drugs used in this study may be able to inspect patient or study records.
If your record is used or disseminated for governmental purposes, it will be done under conditions that will
protect your privacy to the fullest extent possible consistent with laws relating to public disclosure of information
and law-enforcement responsibilities of the agency.
You authorize the use of clinical information, contained in your records, but any publication which includes such
information or data shall not reveal your name, show your picture, or contain any other personally identifying
information, except as otherwise required by law.
Patient Protection
Further information on the risks, benefits or alternative treatments may be obtained from your doctor,
at #
.
This study has been approved by the committee to protect human rights at
Hospital.
Information concerning research subjects rights protection can be obtained by contacting the office of
at #
. If at any point during the duration of this treatment
you feel that you have been inadequately informed of the risks, benefits or alternative treatments, or encouraged
to continue in this study beyond your wish to do so, please contact the office noted above.
In the event of injury or illness resulting from any research procedure, appropriate care will be available to you
including hospitalization if necessary. Financial compensation for the costs of this care is not available.
New Findings
You will be informed of any new findings which may affect your decision to continue participating in this
research study.
Voluntary Consent and Right to Withdraw
Participation is voluntary. You may choose not to participate or you may withdraw your consent to participate in
this study at any time. If you withdraw from the study, you will continue to be followed and clinical data will be
collected from your medical records. Withdrawal will in no way affect your quality of medical care in the future.
No compensation for participation will be given.
Circumstances Under Which Your Participation May Be Terminated Without Your Consent
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There are circumstances under which your doctor might be required to discontinue your treatment whether you
agree or not. These circumstances include: your tumor gets worse despite the treatment; the side effects of the
treatment are too dangerous for you; new information about the treatment becomes available and this information
suggests the treatment will be ineffective or unsafe for you.
Patient Contract
I have been offered the opportunity to ask questions about this study and all questions have been answered to my
satisfaction. The contents of this form have been explained to me and I understand them. I agree to allow the
research personnel specified above the access to my medical records. I also agree to notify my doctor of any
change of address and/or telephone number.
My signature below means that I have voluntarily agreed to participate in this research study. A copy of this
consent form has been given to me.
(Date)
(Date)
9/9/96
(Patient Signature)
(Witness Signature)
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