Unblinding clinical scenarios and Advice

It should be possible to manage most acute clinical situations by assuming a trial participant has been taking either total daily amount of 40mg Telmisartan or 5mg Terazosin and/or by subsequently withholding the trial medication if appropriate.

However, there may be clinical circumstances where knowledge of treatment allocation is essential to guide immediate clinical management. Where unblinding is being considered, ideally the case should be discussed with the local trial Principal Investigator or EJS ACT-PD Trial team, if required and possible. However, this discussion is not mandatory.

IF YOU ARE A MEMBER OF AN EJS ACT-PD TRIAL TEAM UNBLINDING ONE OF THE PARTICIPANTS AT YOUR SITE, PLEASE ENSURE YOU COMPLETE AN SAE FORM WITHIN 24 HOURS.

Guidance on a number of anticipated scenarios with specific advice about the need to unblind: 

Overdose

If the patient is suspected to have overdosed on their IMP, it would be appropriate to first try to gauge how many capsules they have taken.  

Participants who have taken an overdose should be seen in their nearest Accident & Emergency department. Cardiovascular support is of greatest importance. Restoration of blood pressure and normalisation of heart rate may be accomplished by keeping the patient in a supine position. If this measure is inadequate, shock should first be treated with volume expanders and if necessary, vasopressors could then be used. Suggested measures include induction of emesis and / or gastric lavage. Activated charcoal may be useful in the treatment of overdosage. Renal function should be monitored and general supportive measures applied as required. 

If it’s clinically believed that the overdose is sufficient to cause significant symptoms or signs or explain their current clinical picture, then unblinding is appropriate.

Symptomatic orthostatic hypotension

Hypotension, particularly orthostatic hypotension is common in Parkinson’s disease and this may be exacerbated by either Telmisartan or Terazosin use. Blood pressure measurements should not be performed routinely in EJS ACT-PD trial participants but should be performed in any individuals with clinically relevant symptoms potentially explicable by hypotension. Each participant will have been provided with a Blood pressure measuring device and instructed on its use.

The approach to treatment of orthostatic hypotension depends on its severity and/or the presence of clinical symptoms:

-advice on adequate oral hydration

-advice on adequate dietary salt/ sodium supplements.

-rationalisation of other hypotensive medications.

-use of thromboembolic compression stockings

-addition of oral anti-hypotensive agents e.g, fludrocortisone, midodrine.

-temporary pause of trial medications during inter-current illnesses.

In an acute setting, the participant should be instructed to sit down or lie down. If persistent symptoms despite above clinical advice, the participant should stop trial medication. There is no need to unblind the patient in this scenario.

Significant hyperkalaemia

This is a potential side effect of Telmisartan. Serum potassium above 5.5 mmol/L should be investigated, and levels above 6.5 mmol/L are considered an emergency. Ensure laboratory results are not due to haemolysis of a sample during blood collection.  If a persistent, significantly elevated potassium level occurs (K+ > 5.5mmol/L) without a suitable alternative explanation e.g. introduction of ACE inhibitor or potassium sparing diuretic, then unblinding is appropriate.

Cataract surgery

Terazosin is associated with a condition called Intraoperative Floppy Iris Syndrome (IFIS) which can complicate cataract surgery and increase the risk of complications. It is crucial to inform the ophthalmologist about the patient’s trial participation, and that includes the possibility of terazosin use before undergoing cataract surgery. If the ophthalmologist advises, a treatment pause is mandated around the time of cataract surgery, as per the study protocol, rather than unblinding.  There is no need to unblind the patient in this scenario.

Priapism

Terazosin can cause a painful erection (priapism), which cannot be relieved by having sex or masturbation. If this happens, get medical help immediately. If priapism occurs without a suitable alternative explanation, then unblinding is appropriate.