Randomized Trial of Ivabradine in Patients With Hyperadrenergic [POTS], 2021, Taub et al

[EndME]

Agreed, although I don't think this breaks blinding any more than noticing an effect on heart rate and wellbeing might.

I'm not entirely sure on that. You also have the additional problem of unblinding the PI, which I see no reason for introducing. Some of this will also depend on how much information was fed back to the participants.

I agree they probably had justified resonse for a dose titration protocol. I don't think that is an issue. Additional problems occurring with blinding there could have probably been avoided to some degree by not feeding back any information to the patients as part of that and having the titration and measurements being taken by someone independent.

Regarding the number of dosage changes I'm thinking that this misses important details. From what I see only changes for the active drug are reported. That misses the point I made above. I'm not entirely sure about things either though.

 

[Utsikt]

They say that every one of them did a tilt table test at the start that confirmed POTS.

Some of them did not have POT during the 3 min standing test but that doesn't mean they don't have POTS...

Figure 1 says they used HUTT for the day 0 measurement.


If they actually used OMV for the measurements in table 1 and 2, they should probably have labeled it better.

It also begs the question of why the only did the OMV for 3 minutes?

 

[Eddie]

I'm not entirely sure on that. You also have the additional problem of unblinding the PI, which I see no reason for introducing. Some of this will also depend on how much information was fed back to the participants.

I agree they probably had justified resonse for a dose titration protocol. I don't think that is an issue. Additional problems occurring with blinding there could have probably been avoided to some degree by not feeding back any information to the patients as part of that and having the titration and measurements being taken by someone independent.

Regarding the number of dosage changes I'm thinking that this misses important details. From what I see only changes for the active drug are reported. That misses the point I made above. I'm not entirely sure about things either though.

I think does introduce some valid criticisms. I'm imaging being a study participant and going in and them saying we are going to up the dose. That might suggest you are in the placebo group but it could also be equally valid that the dose of the real drug was too low to produce a response.

I get the impression that they weren't changes does all over the place in either arm, but I agree it is a little unclear for the placebo.

 

[Eddie]

If they actually used OMV for the measurements in table 1 and 2, they should probably have labeled it better.

It also begs the question of why the only did the OMV for 3 minutes?

For sure, the table labeling confused me too. Given they excluded people for not reaching the 30 bpm I think it has to be the case that those results are from the standing test.

Because a full on TTT is pretty intense. Given they did a TTT during the screening you would think it might make sense just to run another two at the end of each treatment. But it also a little unnecessary if you have already confirmed these people fit the POTS criteria and care more about the difference in HR between placebo and controls. At least that is my guess in the thinking and seems reasonable.

 

[Utsikt]

But it also a little unnecessary if you have already confirmed these people fit the POTS criteria and care more about the difference in HR between placebo and controls.

If the POTS criteria says «within 10 minutes» and they only measure «within 3 minutes» for the trial measurements, they are measuring a HR that isn’t directly relevant for the criteria.

I don’t think that makes any sense at all.