Background
“The Got-it trial is a randomised placebo controlled double blind pragmatic UK-wide RCT involving women who have a retained placenta (RP) recruited from delivery wards in UK maternity hospitals. RP is a major cause of postpartum haemorrhage and affects around 2 % of vaginal deliveries in the UK. It is diagnosed when the placenta is not delivered within 30 minutes following active management or 60 minutes after physiological followed by active management of the third stage of labour after delivery of the baby [26]. Although some placentas can still be delivered vaginally after a RP is diagnosed, the chance of this happening is low and decreases the longer the placenta remains in situ. The definitive management of RP is, therefore, manual removal of the placenta which is a surgical procedure requiring trained personnel and an operating theatre. The aim of the Got-it trial is to determine whether use of glyceryl trinitrate (GTN) spray, as compared to a placebo, can facilitate delivery of the placenta without having to undertake manual or surgical delivery in theatre. GTN is a drug that was originally developed for the prevention and relief of angina attacks. Its side-effects include headache, dizziness, flushing/feeling hot, a drop in blood pressure or a rise in pulse. In the clinical context of RP, it could also affect blood loss due to its primary mode of action as a muscle relaxant. For the trial’s inclusion and exclusion criteria see Lawton et al. [17]. |
The trial comprises an internal pilot followed by a substantive RCT. The pilot commenced in October 2014 and involved eight sites that entered the pilot in a staggered way. During the pilot, once a diagnosis of RP had been made, a delegated and trained member of the clinical or research team approached potential recruits. These women were given written information in the form of a one page summary leaflet accompanied by a detailed participant information sheet. Women were also given a verbal explanation of the trial that covered all the elements in the participant information sheet and consent form. Women who gave their consent were randomized to receive GTN or a placebo spray, which they self-administered under their tongue (two puffs). The placebo spray was designed to be identical in taste and appearance to GTN so neither participants nor staff could determine the outcome of randomization. Women who did not deliver their placentas within 15 minutes were taken to theatre for manual removal of the placenta under regional or general anaesthesia, with the method of anaesthetic being determined by the clinical team and being dependent on the urgency of need for placental delivery.” |
Excerpts from Lawton et al. [17] |
The role of hope, therapeutic optimism and uncertainty in clinical research
Characterising therapeutic optimism in clinical research
Methods
Study aims
Study setting
Ethical approval
Recruitment
Data collection and analysis
Results
Interview participants
N = 27 | Percent | |
---|---|---|
Obstetricians | 10 | 37 |
Clinical midwives | 6 | 22 |
Research midwives | 11 | 41 |
Education | ||
Professional qualifications | 1 | 4 |
Degree | 26 | 96 |
Higher degree | 5 | 19 |
Time in current post (years) | ||
0-2 years | 9 | 41 |
2.5-5years | 13 | 48 |
5.5-10 years | 2 | 7 |
> 10 years | 3 | 11 |
No previous research experience | ||
Research midwives | 0 | 0 |
Obstetricians | 4 | 15 |
Midwives | 2 | 7 |
Accounting for uncertainty: initial perceptions of trial design
Research midwife O: See the big thing really for us has been the hospital staff being on board…They’ve been really really good. They’ve been watching out for patients so even when we’re not physically here they’re actually, you know, they’re helping us with recruitment. … ‘cause without them on board we’d not get anywhere with it.
Dr D: …it’s plausible that it might work. I’ve seen GTN used in other emergency situations in uterine inversion. We couldn’t get the uterus back in. We used GTN to relax the uterus. So I can see the physiology of why it’d work. I don’t know if it will though (laughs). I suppose that’s why we’re doing the study.
Dr A: I have given GTN to try and relax the cervix, whether it’s that mechanism… I don’t know for sure so I believe there is some effect with muscle and things so I can see that, you know, potentially it will, it could have an effect and therefore, I definitely think it’s worth trying. But I don’t think we know.
Yeah, it’s definitely a good, good idea, and the thinking about behind it is fairly reasonable as well, in terms of using GTN to relax the uterus to deliver the placenta. Yeah, so I think it’s a really good trial.
Clinical midwife C: But to be honest, I think the only incentive that I, or any midwife, would need is the possibility that it might work. And that you might be avoiding a trip to theatre — no one wants a trip to theatre, no one: the midwife doesn’t want a trip to theatre, the doctor doesn’t and the woman certainly doesn’t. So we’re all working towards the same ultimate goal, to get the placenta out without going to theatre. So for me, that’s all the incentive I need, I would do anything to get that placenta out without going to theatre.
Familiarity breeds therapeutic optimism: perceptions of the study drug
Dr E: I think it helps staff, or it brings up more questions I guess, ‘cause staff are thinking they know what the drug is. So they’re instantly thinking, well GTN does that. Ooh we’re doing the opposite to what we normally do with oxytocin we make everything contract, we’re getting everything to relax… It just makes it more accessible I guess, in the sense that people recognise the drug, so instantly can start to hypothesise what the rationale is for the trial, without reading anything.
Dr H: It’s a lot easier actually to talk about a drug that you’ve got quite a lot of knowledge and experience and has been around for a long time than something new that all you’ve got is theoretical knowledge that you’ve been told.
Constructing therapeutic optimism: perceptions of clinical need
Research midwife M: I think the benefits of it [GTN], if it did work, would save such a lot of time, inconvenience, pain for the woman, distress and separation. And there are so many benefits I think the midwives are keen to do it. The way they say, ‘if it does that, and prevents all that, how good this will be’. And especially for the future, if it does work, being able to use in birth centres and community settings. Yeah the benefits of it will be really good if it did just have an effect.
Research midwife G: I think if it [GTN] can prove to work, then fantastic. It’s definitely worthwhile trying it and seeing, you know, where it comes from. Cause I think anything that can stop the women to have — a manual removal’s just awful. And I think when you’ve seen a few, it’s so barbaric you feel like you’re on a farm. Poor woman, watching them go through that. So I think anything that can be shown to stop that having to happen, then fantastic.
Dr I: From the doctor’s point of view, you know, it’s obviously better for the woman as well, less risk and less medicalisation the day after. But it’s also less work. You can concentrate, focus on women who are in labour, or who may be sick or you know, other women.
Clinical midwife N: I hope it does… if it works it will be amazing because it will reduce these women going to theatre for such an invasive procedure …if it works it will be amazing because it will keep families together.
Research midwife H: I think, with this trial in particular, because it is to do with retained placentas. And the midwife, you know, often does feel bad when they have to go to theatre. And you do question, could I have done anything different that would have changed the outcome. So by having some other option, rather than theatre, I think lots of midwives feel, you know, we really want to try this.
Maintaining therapeutic optimism and sustaining trial recruitment
I: Is it working so far?Dr I: Yes I think so. And the staff think so. Because they think they can smell the drug. But obviously that’s just in their head. The Band 6 midwives have said as soon as the puffs are given it seems to come out. I think one midwife’s been involved in two cases, well we’ve only — done six or seven, so you know. But I think it will show something…And I think from what I’ve seen it seems to work. …I think, the way the drug works, it should — I’m hoping it’ll work. And I think it will. That’s just because of the drug characteristics and a little bit of what I’ve seen.
I: Do you feel that helps once there’s a success?Dr H: When we had that one everybody was really excited and I think fairly shortly after that we randomised quite a lot more people.
Research midwife A: In [site] there’s been seven [randomisations]. So far all our ladies have unfortunately gone to theatre. However, I think about three of them the placenta has been sitting in the vagina when they’ve got there. So, we would, well I — would assume that they possibly have had the drug rather than the placebo as opposed to the ladies that have gone on to need a proper manual removal, it suggests that they’ve possibly had the placebo.
Research midwife I: I think we may have six or seven [recruits], and then it’s only one that’s been successful. …I’m not sure why, I don’t know the reason. They might all be placebos they’re getting. Or it may not work. It’s hard to say, isn’t it? But, we just feel a bit disheartened really. And it kind of drops the morale with the staff a little bit as well, when you just keep getting a bit of a negative result with it. And we think that staff might start to think, is there any point in doing the Got It trial. It’s not going to work … I just feel it would be nice if we got some positive results to kind of encourage staff a little bit more.
Research midwife G: ‘Cause we’ve had quite a few PPHs. And obviously, we don’t know if it’s linked or not. But it’s put a lot of the midwives, and doctors [off] …when they talk, quite candidly, then they will be honest and just say, well it does put them off, because they don’t want to go in — a woman that’s quite nice and stable, and then they seem to take two puffs of this and they suddenly start bleeding and it becomes an emergency situation, rather than a calm situation that needs dealing with. It seems that, a few of them have had that repeated experience and it’s just really put them off.