1. A guide to STREAM trial medicines:
Know your medication!

2. Overview STREAM trial design and medicines
Information for participants
How to store trial medicine
What to do with extra medicine
How to take trial medicine
Strategies for improving medication adherence
Possible side effects and interactions of trial medicines

3. STREAM trial design and medicines

4. STREAM trial design
Participants randomly assigned to 4 treatment groups or “arms” (A,B,C and D)
Arm A => national guidelines for MDR-TB
Arms B,C and D => different combinations of available MDR-TB medicines (oral and injectable) for 6 or 9 months
Aim to evaluate the effectiveness of shorter treatment regimens for MDR-TB
New medicine – Bedaquiline (Sirturo®) – added to some arms
Bedaquiline is the first new medicine in over 50 years for the treatment of tuberculosis
Approval from US Food and Drug Administration - December 2012
Conditional marketing authorization from European Medicines Agency

5. STREAM Trial Medicines

6. STREAM Trial Medicines
Participants are randomly assigned to 4 different treatment groups (A,B,C and D)
B,C and D use combinations of 6 or 7 different medicines in the intensive and continuation phases of treatment
Bedaquiline is included in regimens C and D
Varies by country B
40 weeks C
40 weeks D
28 weeks

7. STREAM Trial Medicines
Depending on treatment group, participants may take up to 19 pills every day during the intensive and continuation phases of treatment.
Participants in group B and D also have injections.

8. Information for participants

9. How to store trial medicines
Properly storing trial medicines helps limit exposure to damaging effects and assure their integrity and quality
Trial medicines should be stored safely and securely out of the sun, away from the sink/basin and hot appliances
Trial medicines should be stored in a cool, dry place
For example, medication should not be stored in the bathroom. Heat and moisture from the sink, bath and shower may damage tablets
Be sure to store trial medicines so that insects and animals can’t reach them

10. How to store trial medicines
Trial medicines should be stored out of reach of anyone other than the patient and his/her DOT supporter
PLEASE, always store medicines away from children and teenagers to prevent accidents

11. What to do with extra medicine
If a participant has extra pills (for example, due to missed doses), they must take the extra pills with them to their next doctor’s visit:
Doctor can properly dispose of them
Doctor can monitor adherence

12. How to take trial medicines
Participants should take trial medicines only as directed by the STREAM trial team
This will ensure participants complete the recommended course of treatment and achieve maximum benefit from participating in the trial
Participants should continue to take trial medicines even when they feel better or notice their symptoms get better
Participants should NOT stop taking trial medicines without first consulting the STREAM trial team

13. How to take trial medicines
should be taken with food
should be swallowed whole with water
should not be chewed or crushed
should not be shared with anyone

14. Strategies for improving adherence
“Medicines don’t work in patients who don’t take them.”
Dr. C. Everett Koop, MD, US Surgeon General ( )

15. Factors that influence adherence
Factors that could make it harder for participants to take their trial medicines properly include:
Complexity of their treatment
Side effects of treatment
Not understanding their illness
Not understanding how trial medicines should be taken
Substance abuse
Trouble in swallowing
Language barriers
Forgetfulness
Religious or cultural beliefs

16. How to improve adherence
A few things can be done to improve treatment adherence in STREAM participants
STREAM trial staff should explain to participants:
Why each trial medication is being used
The potential benefits and side effects of the medicine
The potential for the development of resistance if not all the medication is taken
How to properly store medications
What to expect upon completion of treatment
How response to treatment is measured

17. How to improve adherence
STREAM trial staff should identify patients who miss visits or don’t take their medicines early and respond quickly with supportive care
Participants can develop ways to remember to attend their visits and take the right dosage of their medication at the right time – e.g. pill boxes; alarm clocks; calendars; enlist support from family, friends or caregivers; establish a routine, i.e. take meds before your daily morning coffee or breakfast

18. Side effects
STREAM trial medicines have the potential to cause a variety of side effects and therefore STREAM trial staff will monitor participants carefully to identify side effects and respond to them
Some of the tests participants will undergo to identify side effects include:
Blood tests
Hearing tests
ECGs to measure heart rhythm
Vision tests

19. Common side effects Nausea Vomiting Diarrhea Headaches
Numbness and pins and needles in feet
Tingling
Joint Pains

20. Side Effects
Participants should notify the STREAM trial team if they have new side effects or if their side effects continue or get worse
If a patient has an allergic reaction, like rash, hives, itching, shortness of breath, wheezing, cough, swelling of the face lips, tongue, or throat, they should seek medical attention immediately
Some side effects can be serious, e.g. hearing loss and kidney failure
Other side effects may go away as the patient’s body adjusts to the medicine, e.g. nausea
Participants should ask the STREAM trial team what to do if they vomit within 30 minutes of taking trial medicines

21. Drug interactions
The STREAM trial team should ask about all non-trial medicines participants are taking including prescription medicines, over the counter and herbal medications
Helps the trial team to mitigate and monitor for drug interactions
Participants should not take over-the-counter medications, herbals, vitamins or traditional medications during the STREAM trial without first consulting the trial team

22. Drug interactions
Foods that may interact with the STREAM trial medicines include:
Oranges
Grapefruit
Tuna
Aged Cheese
Smoked or cured meat
Alcohol
To avoid interactions, participants should ask their trial doctor or pharmacist about required changes to their diet

23. Pregnancy
Medicines can be transferred to babies via breast milk or may interfere with development of babies during pregnancy
We do not know if the medicines in STREAM are safe during pregnancy
Female participants must notify the STREAM trial team if they think they may be pregnant. Women who fall pregnant during the trial will be discontinued from trial medication and will complete their treatment as part of the National TB program.

24. Reminders
A patient’s STREAM treatment will depend on which treatment group (A,B,C and D) they are in
Participants should store and take trial medicines as directed by the STREAM trial team
Remember, medicines only work if they are taken
Participants should talk to the STREAM trial team if they have any questions about their treatment or if they have any side effects from taking their pills

25. Thank you!