Thread by @Dan_Engelman

Thrilled and delighted to be a part of the GOAL trial team – published in @NEJM this week.
nejm.org/doi/full/10.10…
What is the GOAL trial and what does it mean? A thread.
1/🧵

GOAL stands for GwokO Adunu pa Lutino meaning “Protect the Heart of a Child.” ❤️🩺🚸
This trial tested a new strategy to prevent premature death and disability from Rheumatic Heart Disease #RHD 2/

RHD causes >300,000 annual deaths & enormous morbidity, esp in LMIC countries, Indigenous and disadvantaged communities. Many are children or young adults in their prime. Most present with advanced disease, so little opportunity for intervention. 3/
nejm.org/doi/full/10.10…

We have known for around 15 years that early signs of RHD can be detected using echocardiography (ultrasound) before clinical disease is apparent. 4/
nejm.org/doi/full/10.10…

This advance led to a large number of screening and prevalence studies in many LMIC – revealing a MUCH larger burden of RHD than previously known. 5/
thelancet.com/journals/langl…

Advances in RHD screening research have shown brief echo / focused US to be a safe and accurate test; amenable to task shifting to nurses and other health workers. 6/
thelancet.com/journals/langl…

So, we could find LOTS of undiagnosed, early RHD. We also knew that prophylaxis (usually IM benzathine penicillin) improves outcomes for pts w rheumatic fever. But we DIDN’T know if it would improve outcomes for latent RHD detected through screening. 7/
nature.com/articles/nrcar…

The GOAL trial was led by @emmyrov @HeartUganda Andrea Beaton @CincyChildrens Craig Sable @ChildrensNatl Andrew Steer @MCRI_for_kids with many local investigators and international researchers supporting. 8/

In the trial, >100,000 children were screened using #Echo / #FOCUS in the Gulu District of northern #Uganda. This was an undertaking on a massive scale and an incredible achievement in itself. 9/

409 children were randomized to 4-weekly IM BPG injections. 409 were randomized to no treatment. Groups were similar at baseline. Both groups received extensive education and peer-support - another ground-breaking advance. 10/
doi.org/10.1016/j.pec.…

The primary outcome looked at progression (worsening) of RHD on echocardiogram at 2 years. Regression (improvement) of echos was a secondary outcome.
Echo adjudication was by a blinded, consensus panel using a robust process. 11/
doi.org/10.1016/j.ijca…

What did we find?
>97% completed the trial – despite the huge challenges of COVID-19 pandemic.
In the prophylaxis group 3/399 progressed (0.8%)
In the control group 33/400 progressed (8.2%)
RR 0.09 (CI 0.03-0.29) P<0.001
12/

This means: For every 13 children commenced on prophylaxis, 1 case of progression at 2 years was prevented (NNT=13, 95%CI 10-21). This is the first evidence suggesting that secondary antibiotic prophylaxis can improve outcomes for children with latent, screening-detected RHD. 13/

Sec outcome: About half of each group normalized in each group - no difference. Two SAEs were attributable to the intervention.
As yet, we are unable to determine which children are at higher risk of progression. (More work to come on the detailed echo findings.) 14/

Important caveat: GOAL trial achieved remarkable adherence with prophylaxis – around 99%. This is almost unheard of, and a testament to the dedication of children, families and study teams. 15/

However, such adherence has not been achievable in other LMICs or even high-income places like Australia. Here is 1 example from Fiji showing low adherence after screening. Screening itself is not an intervention – strong health systems are required. 16/
doi.org/10.1111/tmi.12…

Effectiveness in other settings with lower adherence remains unknown but would almost certainly be more limited (higher NNT). 17/

On a personal level, involvement in this trial has been deeply rewarding. I started collaborating with Drs Beaton, Okello, Sable et al in 2013, when we developed and tested modules for training RHD Echo. 18/
wiredhealthresources.net/EchoProject/

The whole team has worked in true partnership with communities, clinicians and academics of #Uganda to complete a remarkable trial. Further studies planned to address some of the outstanding questions! We need to, and will do more to #EndRHD
END 🧵