The Shenfu Trial


 

 

Efficacy and Safety of Combination Therapy of Shenfu Injection and Postresuscitation Bundle in Patients With Return of Spontaneous Circulation After In-Hospital Cardiac Arrest, by Zhang et al. [1]

 

We all remember Mr. Miyagi’s lessons: clean the cars, paint the fences, and all those crazy stuff Daniel San couldn’t understand. Classic movie. I don’t know if you remember, but Daniel San hurt his leg just before his final fight at All-Valley Karate Tournament. How was he suppose to fight that “Cobra Kai” blond guy? I can’t even remember his name. Miyagi then clapped his hands, and after a little bit of this, a little bit of that and some old ancient oriental magic, Daniel San was good to go! Spoiler alert: Daniel San won the fight!

Last year I wrote a post about vasopressin (here) and how we doctors, sometimes, are like alchemists. Always trying to find that one missing piece of a puzzle that somehow could cure everything. Vitamins, statins, N-Acetylcistein, hypothermia… Quite an aggressive post I might say, with undesired repercussions. Anyway. As the alchemists, we never found that miracle drug that could cure everything and save everyone. We are unable to turn patients into gold yet.

Few months later Paul Marik, that crazy fellow we all love, published his retrospective paper revealing the possible cure for sepsis[2] with a combination of vitamin C, steroids and vitamin B1. Not a single sepsis related death in 7 months. OMG! Scientific community went crazy! Heliox Parties again! However, here we are, still waiting for a big trial to confirm or refute his hypothesis.

Last month, Critical Care Medicine published a new trial, with the promess to shake critical care world again! The Shenfu Trial[1], investigating a drug that experimental trials showed scavenged free radicals and suppressed the inflammation pathways and apoptosis.

But what the hell is shenfu?

Shenfu is a drug used in oriental medicine, based on ginseng and aconinte[3]. Never heard of it before this trial. But we already have a meta-analysis[4] showing mortality benefits in sepsis. Well, some Chinese scientists decided to run a big RCT investigating the potential benefits of shenfu on a specific condition still lacking good treatment: post cardiac arrest syndrome.

Just to remember the challenge: “for every eight attempted resuscitations there were three immediate survivors, two at 24 hours, and one alive at one year”. This was published in 1992 [5] and until today there were no big advances in this field.

How the did it:

They prospectively randomized 1022 patients (Chinese trial with less than 1000 patients are usually considered pilot studies) with sustained return of spontaneous circulation after in-hospital cardiac arrest to either standard care or standard care plus shenfu 100 ml b.i.d for 14 days or until hospital discharge! How cool is this name, right? I really want to prescribe some shenfu to my patients. Or not. The primary outcome was 28-day survival rate (Hard!).

Sooooouuuunnnds goood?! Really good trial design. But there’s always a but! This was an open label study. Since shenfu is yellow, the investigators “couldn’t” blind the caregivers. The participants (?) and the outcome accessors were blinded. It seems China is unable to produce a yellow placebo. They re planning a fucking trip to the moon but they can’t do a miserable yellow placebo! C’mon! Therefore, there were no placebo!

Anyway. We still can analyze the data. We’re talking about a hard outcome, mortality, that’s interesting. Although this study remembers me that bling guy begging for money, and after you give him 5 buck he looks at the bill and say: “Five bucks? You cheap bastard!”

What they found:

Randomization did its job! There were no differences between groups, including arrest etiology, rhythm and duration. Also the drug appears to be safe, with no relevant side effects in this trial. But let’s finally cut this cheese! Well, dear friends, Shenfu seems to be a slap in our ugly ocidental faces! Primary outcome (28d survival) was experienced in 42.7% in intervention group vs 30.1% in placebo, I mean, in standard care alone!

Zhang Q, Li C, Shao F, Zhao L, Wang M, Fang Y. Efficacy and Safety of Combination Therapy of Shenfu Injection and Postresuscitation Bundle in Patients With Return of Spontaneous Circulation After In-Hospital Cardiac Arrest Critical Care Medicine. 2017.

This is HUGE! A 12% difference in survival rate is amazing! The ARMA trial [6], arguably the most discussed trial in critical care, showed a mortality benefit of 8-9%! Not only that! The secondary outcomes pointed to something that could be a game changer! Something that could solve our alchemist puzzle and turn patients into gold: neurological improvement!

Zhang Q, Li C, Shao F, Zhao L, Wang M, Fang Y. Efficacy and Safety of Combination Therapy of Shenfu Injection and Postresuscitation Bundle in Patients With Return of Spontaneous Circulation After In-Hospital Cardiac Arrest Critical Care Medicine. 2017.

Secondary outcomes also showed a decrease in multiple organ disfunction and lactate levels, probably related to the drug’s action mechanism.

To wrap it up:

Although I’m always sceptic about miracle drugs, it seems we might have something here. As our fellows from TheBottomLine said: “the sceptic in me tells me that if something appears too good to be true then it probably is”. It doesn’t work every time. I’ve been fooled in online shops a few times.

I think the blinding problem, or the lack of it, could impair the analysis of secondary outcomes, but there is a signal about mortality we can’t deny. Does shenfu contains vitamin C? Shenfu is a promising drug, which has really cool name and I am certain it will be desired by alchemists. I’m certain also that soon enough it will be tested for every neurological condition, sepsis and many other diseases. International studies to proof that shenfu works despite faith and country are needed. And please, Ray Charles blind it! Shenfu might be crawling, but as Myiagi would say: First learn to stand, then learn to fly. Natural rule Daniel San, not mine.

 

 

1.     Zhang Q, Li C, Shao F, Zhao L, Wang M, Fang Y. Efficacy and Safety of Combination Therapy of Shenfu Injection and Postresuscitation Bundle in Patients With Return of Spontaneous Circulation After In-Hospital Cardiac Arrest Critical Care Medicine. 2017.
2.     Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock Chest. 2017; 151(6):1229-1238.
3.     Luo J, Min S, Wei K, Cao J. Ion channel mechanism and ingredient bases of Shenfu Decoction’s cardiac electrophysiological effects Journal of Ethnopharmacology. 2008; 117(3):439-445.
4.     Wen-Ting S, Fa-Feng C, Li X, Cheng-Ren L, Jian-Xun L. Chinese Medicine Shenfu Injection for Heart Failure: A Systematic Review and Meta-Analysis Evidence-Based Complementary and Alternative Medicine. 2012; 2012:1-25.
5.     Tunstall-Pedoe H, Bailey L, Chamberlain DA, Marsden AK, Ward ME, Zideman DA. Survey of 3765 cardiopulmonary resuscitations in British hospitals (the BRESUS Study): methods and overall results. BMJ. 1992; 304(6838):1347-1351.
6.     The Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome N Engl J Med. 2000; 342(18):1301-1308.

 

 

Photo credit

Karate Kid


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The Shenfu Trial

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