Drugs for reducing stomach acid for people with cystic fibrosis

Review question

We reviewed the evidence for using drugs to reduce stomach acid in people with cystic fibrosis.


Cystic fibrosis causes damage to the lungs and the pancreas. The pancreas produces enzymes which are needed for the body to digest and absorb food. If the pancreas is damaged this can affect how people can absorb food. It can also increase acidity in the stomach, which may lead to heartburn and peptic ulcers. There are drugs that can reduce the amount of acid in the stomach. Trials of these drugs have shown that they can improve problems in the stomach and digestive system and in the absorption of fat. This is an updated version of the review.

Search date

The evidence is current to: 26 April 2021.

Study characteristics

The review included at 17 trials with a total of 273 children and adults. Seven of the trials were limited to children and four trials enrolled only adults, while the remainder enrolled people of any age. All the trials were run in single centres and lasted from five days to six months.

Most trials compared an intervention to placebo (a dummy treatment with no active medication). Six trials compared proton pump inhibitors (drugs which reduce the amount of acid made in the stomach, e.g. omeprazole and esomeprazole) to placebo and seven trials compared a H2 receptor antagonist (a second group of medicines that reduce the amount of acid made in the stomach, e.g. ranitidine and cimetidine) to placebo. One of the trials had three arms and compared a proton pump inhibitor to both a H2 receptor agonist and a placebo. In the remaining five trials, one compared pancrelipase (a combination of three enzymes (lipase, protease, and amylase) normally produced by the pancreas) to a combination of pancrelipase and misoprostol (a drug which protects the lining of the gut from stomach acid); one compared misoprostol to placebo and one trial compared enprostil (similar drug to misoprostol) to ranitidine. Two trials used sodium bicarbonate - one compared to placebo and the second compared to calcium carbonate.

Key results

We were not able to combine the results from these trials due to their design. Individual trials reported some improvements in abdominal pain and fat absorption. However, the trials did not report improvements for other outcomes such as lung function, quality of life, or survival. The different drugs studied caused some adverse events; mainly diarrhoea (two people withdrew from one trial because of this) and bloating due to wind. As we could not combine the results from these trials, we were not able to reach firm conclusions about whether people with cystic fibrosis would benefit from taking these drugs. New long-term trials are needed to examine the benefits and possible adverse effects for people with cystic fibrosis taking drugs to reduce stomach acid.

Quality of the evidence

There were 14 trials which had a cross-over design (where people taking part are given first one treatment and then another treatment) and we did not have the appropriate information to analyse the results properly. Few of the included trials reported clearly on aspects of trial quality or gave enough information to allow us to judge whether any factors might cause a potential risk of bias to the results.

Authors' conclusions: 

Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

Read the full abstract...

Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.


To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.

Search strategy: 

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic and non-electronic database searches, handsearches of relevant journals,  abstract books and conference proceedings. Both authors double checked the reference lists of the searches

Most recent search of the Group's Trials Register: 26 April 2021.

On the 26 April 2021 further searches were conducted on the clinicaltrials.gov register to identify any ongoing trials that may be of relevance. The WHO ICTRP database was last searched in 2020 and is not currently available for searching due to the Covid-19 pandemic.

Selection criteria: 

All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.

Data collection and analysis: 

Both authors independently selected trials, assessed trial quality and extracted data.

Main results: 

The searches identified 40 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.

However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.