Clinical trial NCT02272725: Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
Official title: Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Kidney Injury
Exercise-associated Hyponatremia
Perceived Exertion
Keywords: ultramarathon
ibuprofen
acute kidney injury
exercise-associated hyponatremia
exertion
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2014-10-23
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated hyponatremia (EAH) during an ultramarathon foot race. There is currently much debate over whether NSAID ingestion during endurance events contributes to acute kidney injury. Endurance events often ignite a "perfect storm" of physiologic insults- heat stress, dehydration, and myopathy- which can all negatively impact kidney function. There is a concern that NSAIDs may further potentiate these negative effects as well as contribute to EAH through its anti-diuretic affect. To date, no powered, prospective study has ever examined the effects of NSAIDs on either of these two biochemical outcomes

Ultramarathon endurance events, defined as any race longer than a marathon (26.2 miles), are increasing in popularity, with a 10% increase in annual participants, and more than 69,000 finishers worldwide in 2013. Considerable literature has documented alterations in serum biochemical profiles of these endurance athletes, with consistent evidence of elevated serum creatinine (Cr) levels in healthy race finishers as well as those seeking medical care. While acute renal failure in ultramarathon runners is a rare occurrence, acute kidney injury is common, ranging from 34% in a single-stage ultramarathon to 55-80% in multi-stage ultramarathons. The evidence is equivocal regarding NSAID ingestion and AKI. One study showed that runners who ingested NSAIDs prior to marathons had greater post-race creatinine levels than matched controls as well as higher rates of hospitalization and acute renal failure. However, this contrasts with several other studies that showed a marked lack of difference in creatinine levels or development of acute kidney injury between NSAID users and non-users during ultramarathons. The only randomized trial to date on this subject found no difference in serum creatinine levels between the NSAID and placebo groups at ultramarathon race end, however conclusions were limited by a small unpowered sample size.

Exercise associated hyponatremia (EAH), defined as a serum sodium concentration below 135mEq/L, is recognized as a relatively common issue in endurance running events. The incidence of EAH varies depending upon the distance of the race, with reported values of 3-28% for marathons, 23 - 38% for triathlons and 4-51% in single-stage ultramarathons. EAH is likely under-diagnosed as athletes are often asymptomatic. While EAH most often manifests as non-specific symptoms such as nausea, vomiting, dizziness, and fatigue, it can be a potentially fatal disease that can progress to encephalopathy, seizures, pulmonary edema, and death. There have been no large prospective studies examining the relationship between EAH and NSAID ingestion.

Detailed description: This study will be conducted during the fifth stage of a 6-stage ultramarathon foot race that covers a total of 250 kilometers. Data will be collected during four separate events over the course of the coming year. All races are run by the RacingThePlanet™ 4-desert race series with locations including: Jordan, Ecuador, China, and Chile. The evening after stage 4, participants will be reminded to check in at the medical tent prior to stage 5 start, and at that time the participants will be weighed and given their study drug packet (ibuprofen or visually identical placebo). Approximately 80% of the finishers complete the 80-kilometer Stage 5 in less than 19 hours, so the majority of participants will ingest 1600mg of ibuprofen (400mg q 4 hours x 4 doses). The optimal adult dosing for analgesia is 400mg every 4 hours, with a maximum daily dose of 3200mg ((1999). Product information: Motrin™, ibuprofen. Kalamazoo, MI, Pharmacia \& Upjohn Company.)

Immediately after crossing the finish line of Stage 5, participants will be reweighed, then seated in the study tent where a fingertip blood sample will be obtained via lancet and capillary collection tube (Mock, Morrison, \& Yatscoff, 1995) then analyzed for Na, Cr and BUN (utilizing a Chem-8 cartridge) onsite immediately after collection using an iSTAT® point-of- care analyzer (Abbott; East Windsor, NJ). Any participant who did not complete any stage prior to stage 5 will be removed from the competition and the study. Both the point-of-care device and the digital scale will be calibrated for prior to taking measurements. At this point, the study is over and there is no further participant responsibilities.

Eligibility criteria: Inclusion Criteria:

* Any participant in a RacingThePlanet sanctioned event who understands the consent form in English.

Exclusion Criteria:

* Allergic to any form of non-steroidal anti-inflammatory
* Taken a NSAID or steroid in prior 12 hours
* 1 kidney
* Known to be pregnant or suspected to be pregnant

Primary outcomes:
measure: Acute Kidney Injury
timeFrame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Secondary outcomes:
measure: Perceived Exertion
timeFrame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
measure: Exercise-Associated Hyponatremia
timeFrame: participants will be followed through the duration of a 50 mile ultramarathon, an expected average of 18 hours
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Grant S Lipman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lipman GS, Shea K, Christensen M, Phillips C, Burns P, Higbee R, Koskenoja V, Eifling K, Krabak BJ. Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial. Emerg Med J. 2017 Oct;34(10):637-642. doi: 10.1136/emermed-2016-206353. Epub 2017 Jul 5.