PENGUIN

PENGUIN 2020-06-05T16:42:37+00:00

The PENGUIN trial

PENGUIN: perioperative respiratory care and outcomes for patients undergoing high risk abdominal surgery

PENGUIN is the third global surgical randomised clinical trial following on from the success of FALCON and CHEETAH. PENGUIN aims to reduce Surgical Site Infections (SSI) and pneumonia following abdominal surgery in low and middle-income countries.
Pneumonia and SSI are the most common complications following surgery across the world. They are the commonest healthcare-associated infections in low and middle-income countries, placing significant financial costs on healthcare systems. The increased costs can be a major problem in countries with lower incomes where patients often pay for their own treatment.
PENGUIN is an investigator-initiated and investigator-led trial. PENGUIN is funded by the UK National Institute for Health Research (NIHR).

Aims & Objectives

  • Primary Objective

    The primary objectives of the main RCT is to assess whether preoperative 0.2% chlorhexidine mouthwash reduces the rate of postoperative pneumonia at 30-days compared to no mouthwash, and to assess if 80-100% fraction inspired oxygen (FiO2) used during surgery reduces the rate of postoperative SSI at 30-days compared to 21-30% FiO2.

  • Secondary Objectives

    1. To assess the impact of the interventions on secondary clinical outcomes up to 30 days post-surgery including: mortality rates, repeat abdominal surgery to treat complications (oxygen only), repeat abdominal surgery, length of hospital stay, return to normal activities and admission to z critical care unit.
    2. To explore the impact of the intervention on resource usage and additional costs to the secondary health service provider.
  • The recruitment target is 12,942 participants across all centres

Collaborating countries

PENGUIN is an international trial being conducted in multiple NIHR funded countries. Click on the map below to see participating countries.

Trial summary

Safe and affordable surgery and anaesthesia is a global health priority. There is strong evidence that poor perioperative care is a key factor limiting the net improvements in health which could be achieved through improved global access to surgery. One in six patients experience complications after surgery in LMICs, most commonly infections. Surgical complications reduce life expectancy, quality of life, prevent return to work and cause catastrophic expenditure. For patients undergoing major abdominal surgery, complication rates exceed 30%. Seventy million such procedures are performed worldwide each year (excluding caesarean section) making this the most important global cause of post-operative morbidity and mortality.

An important route of bacterial entry into the lower respiratory tract is aspiration of bacteria in oral and pharyngeal secretions during endotracheal intubation. This results in colonisation of the lower respiratory tract, which overwhelms the patient’s mechanical, humoral, and cellular defences to establish infection following surgery. One potential method to prevent pneumonia after surgery may be to ask patients to use an antiseptic mouthwash with 0.2% chlorhexidine prior to anaesthesia. This treatment is very simple and low in cost, making it ideal for widespread implementation in low and middle-income countries. An international consensus statement from 1,000 anaesthetists, intensive care specialists, surgeons, and epidemiologists identified chlorhexidine mouthwash as a potential inexpensive intervention that may reduce perioperative mortality. However, the statement highlighted the need for effectiveness trials testing chlorhexidine mouthwash before it can be adopted into clinical pathways like perioperative care.

World Health Organisation guidelines recommend the use of liberal inspired oxygen concentrations of 80% during surgery and up to four hours after extubation to help prevent SSI. However, many clinical experts question this recommendation and highlight flaws in the evidence on which it is based. SSIs are clearly important being the most frequent healthcare-associated infection in LMICs, affecting one in three patients undergoing contaminated or dirty surgery. The delivery of high inspired oxygen concentrations during anaesthesia is technically difficult and expensive in resource poor settings. There is also some concern that high inspired oxygen concentrations may even increase mortality amongst acutely ill patients. There is an urgent need for high quality evidence across different settings to evaluate the clinical benefits and harms of high inspired oxygen concentrations to prevent SSI.

The trial aims to assess whether either:
1. Preoperative 0.2% chlorhexidine mouthwash versus no mouthwash can reduce the incidence of post-operative pneumonia 30 days after surgery.
2. 80-100% FiO2 (‘liberal’) versus 21-30% FiO2 (‘restrictive’) during surgery can reduce the incidence of post-operative SSI 30 days after surgery.

PENGUIN is an international, multi-centre, pragmatic, outcome assessor-blinded, 2×2 factorial randomised controlled trial, with an internal pilot designed to assess the effect of the trial interventions in low and middle-income countries.

Patients (adult and children) undergoing an elective or emergency midline laparotomy surgical procedure with an anticipated abdominal incision of at least > 5cm in length will be eligible.

Eligible patients will be randomised at the level of the individual in a 1:1:1:1 ratio between:
1. Preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery
2. No preoperative chlorhexidine mouthwash and 80-100% FiO2 during surgery
3. Preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery
4. No preoperative chlorhexidine mouthwash and 21-30% FiO2 during surgery

The PENGUIN trial has a 6-month internal pilot in four countries (India, South Africa, Nigeria and Mexico) which aims to assess:
• If recruitment to the randomised interventions is feasible
• Compliance with treatment allocation
• Patient retention and follow-up

• Adults and children aged 10 years or over (where permitted)
• Elective or emergency abdominal surgery via midline laparotomy with an anticipated abdominal incision of at least 5cm in length
• Written informed consent of patient (signature or a fingerprint)
NB: Age criterion is country specific. Each country decides the lower age limit for the trial. This is dependent on country-specific regulatory approvals. Age eligibility varies by country.

• Patients undergoing caesarean section
• Patients with a documented or suspected allergy to chlorhexidine
• Patient unable to complete postoperative follow-up (not contactable after discharge)
• Previous enrolment in PENGUIN within the past 30 days
• American Society of Anesthesiologists (ASA) grade V patients (expected to die with or without surgery)

Sponsor

The University of Birmingham is the Sponsor of the PENGUIN Trial in all collaborating countries.

International Coordinating Centre

The PENGUIN International Coordinating Centre trial office is at the University of Birmingham Clinical Trials Unit.
Each country will appoint a National Coordinating Investigator (NCI) and National Coordinating Centre (NCC) – the Hub – who will take national responsibility for the study. The Hubs will be responsible for coordinating recruitment from a range of representative local hospitals – Spokes.

Central and National Trial Management Groups

The Central and National Trial Management Groups (CTMG) include those individuals responsible for the day-to-day running management of the trial. This will include the Chief Investigator, lead methodologist, patient representatives and PENGUIN central management staff.

Trial Steering Committee

The Trial Steering Committee provides supervision of the trial and ensures the trial is being conducted in accordance with the principles of Good Clinical Practice and other relevant regulations.

Data Monitoring Committee

The Data Monitoring Committee will give advice on whether the accumulated data from the trial, together with the results from the other relevant research justifies the continuing recruitment of further participants.

Central Trial Management Group (University of Birmingham)

PENGUIN Trial Team

Birmingham Clinical Trials Unit, Public Health Building

University of Birmingham, Edgbaston, B15 2TT

Email: [email protected]

Tel: from UK 0121 414 4762, International +44 121 414 4762

The PENGUIN Clinical trial is supported by the NIHR Global Health Unit on Global Surgery, The University of Birmingham and The Birmingham Clinical Trials Unit

Countries registered to take part in GlobalSurg II

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