Ivy Leaf: Cough Trials in Adults and Children

Table of Contents

1. Why Cough Trials Are Hard to Read
2. The Independent Systematic Review
3. The 9,657-Patient Postmarketing Study
4. Ivy Leaf as the Comparator in a New Trial
5. Children With Asthma: The 2003 Review
6. The 2014 Crossover Trial
7. Reviews of the Paediatric Evidence
8. Multi-Herb Products
9. What the Evidence Adds Up To
10. Key Research Papers
11. Connections

Why Cough Trials Are Hard to Read

Three features of acute cough make it a difficult condition in which to test a medicine.

• It gets better on its own. Most acute coughs follow a cold or acute bronchitis and fade over days to a few weeks without any treatment. In a study with no comparison group, almost everyone improves, whatever they took.
• The outcomes are largely subjective. Cough severity, frequency and sleep disturbance are usually scored by the patient or a parent. Scores like these respond strongly to expectation, which is why blinding (neither patient nor researcher knowing who got what) matters.
• Small differences can be statistically significant without mattering. A large trial can show that one group's cough score fell slightly faster, with a p-value below 0.05, even though patients would hardly notice the difference.

So the questions to ask of every ivy leaf study are: was there a placebo group, was it blinded, how large was the difference, and who designed and paid for the study?

The Independent Systematic Review

A systematic review collects all studies on a question using a pre-set search and judges each one's quality. The most useful one for ivy leaf comes from a German general-practice research group, who updated their own earlier review in 2021. The update searched MEDLINE, EMBASE, the Cochrane Library and trial registries from December 2009 to January 2020 for randomised trials, controlled trials and observational studies of ivy leaf, alone or in combination, for acute upper respiratory tract infections in adults and children (Sierocinski 2021).

What it found

• 6 randomised controlled trials, 1 controlled clinical trial and 4 observational studies met the criteria. The number of randomised trials had grown since the first review.
• All of the studies concluded that ivy leaf extract is an effective and safe option for cough due to upper respiratory infections and bronchitis.
• Three randomised trials reported a more rapid reduction in cough severity and/or frequency with ivy leaf.
• The clinical significance of these effects "appears to be minimal".
• No serious adverse effects were reported.
• The overall quality of reporting was low and the risk of bias was high.

What it concluded

"Ivy leaf preparations are safe for use in cough due to acute URTIs and bronchitis. However, effects are minimal at best and of uncertain clinical importance." The gap between the studies' own conclusions (all positive) and the reviewers' verdict (minimal, uncertain) is the central fact about the ivy leaf evidence. One of the review's authors disclosed co-authorship of a German general-practice guideline on cough.

The 9,657-Patient Postmarketing Study

The largest ivy leaf study is a prospective, open, multicentre postmarketing study. "Open" means everyone knew what they were taking; "postmarketing" means it followed people using an already-sold product in routine practice. 9,657 patients with acute or chronic bronchitis, 5,181 of them children, took a syrup containing dried ivy leaf extract (Fazio 2009).

• After seven days, 95% of patients were reported as improved or healed.
• Adverse events occurred in 2.1% of patients, mainly gastrointestinal (1.5%).
• Among patients who also received other medicines, adding antibiotics showed no extra benefit in efficacy but was associated with a 26% higher relative risk of side effects.

What this design can and cannot show

With no comparison group, the 95% improvement figure cannot be credited to the syrup: acute bronchitis improves over a week in most people anyway. The antibiotic observation is similarly an association, not a trial result, since the patients who were given antibiotics were not chosen at random. What a study of this size does provide is a meaningful picture of how often side effects are reported in everyday use over a short course, and that picture is reassuring.

Ivy Leaf as the Comparator in a New Trial

In South Korea, a widely prescribed ivy leaf extract served as the standard against which a new product was tested. A randomised, double-blind, multicentre phase 3 trial at six Korean hospitals assigned symptomatic patients with acute upper respiratory infection or chronic inflammatory bronchitis to either a combination of ivy leaf and Coptis chinensis rhizome extracts (coded AG NPP709) or a widely prescribed ivy leaf extract, for five days, 118 patients per group (Cho 2026).

• Patients ranged from 2 to 70 years old; mean age was 24.9 years in the combination group and 21.7 in the ivy group.
• The primary outcome, the clinical improvement rate, did not differ statistically between groups (difference 4.3%, 95% confidence interval −8.9 to 17.5).
• Cough cleared in 43.0% versus 40.0% (p = 0.655), and sputum in 34.6% versus 25.5% (p = 0.142).
• Adverse events were similar: 11.0% versus 11.1%, mostly mild (grade 1 or 2).

What this design can and cannot show

A non-inferiority trial asks whether a new treatment is "not unacceptably worse" than an existing one. It found the combination was not worse than ivy extract alone. Because there was no placebo group, it gives no information about how much either product helps compared with no treatment. It does provide controlled, blinded tolerability data for ivy leaf extract: an adverse-event rate of about one in nine over five days, mostly mild.

Children With Asthma: The 2003 Review

Some ivy leaf research has looked beyond acute cough at whether the extract improves lung function in children with chronic asthma. A 2003 review re-analysed original data from randomised trials of ivy leaf extracts in chronic bronchitis. Of five such trials, three were in children and met the criteria (Hofmann 2003):

• one compared ivy leaf cough drops with placebo;
• one compared suppositories with drops;
• one compared syrup with drops.

Outcomes were measured with body plethysmography and spirometry, which are objective breathing tests rather than symptom scores. In the placebo-controlled trial, the drops were significantly better than placebo at reducing airway resistance, the primary outcome (p = 0.04, two-sided), and better descriptively on the other objective measures. Using the drops as a bridge, the authors estimated that syrup and suppositories preserved at least 54% and 35%, respectively, of the drops' effect against placebo.

The reviewers were direct about the limits: "more far-reaching conclusions can hardly be drawn because of a meagre database, including the fact that only one primary trial included a placebo control." They called for further research, especially on long-term effects.

The 2014 Crossover Trial

A decade later, a German group ran a better-designed test of the same idea: a double-blind, placebo-controlled, randomised crossover trial in which each child received both ivy leaf extract and placebo, in random order, separated by a wash-out period (Zeil 2014).

• Who: 30 children, median age 9.07 years (range 6–11), with mild persistent allergic asthma that was only partly controlled or uncontrolled despite long-term inhaled steroid treatment at 400 μg budesonide equivalent.
• What: after a four-week run-in, four weeks of ivy leaf dry extract or placebo added to their usual inhaler, then a wash-out, then the other treatment.
• Primary outcomes: the relative change in FEV₁ (how much air can be blown out in one second) and MEF_75-25 (a measure of flow in the smaller airways) before bronchodilation. No treatment effect was detected in the crossover analysis (p = 0.68 and p = 0.70).
• Secondary outcomes: some flow and volume measures improved significantly after ivy leaf (for example MEF_75-25 by a mean 0.115 l/s, p = 0.044) but not after placebo.

The authors described it as a proof-of-concept study suggesting that such children "might benefit" and called for further studies. The design's own pre-specified answer, however, was negative: on the outcomes the trial was built to test, ivy leaf did no better than placebo. Secondary outcomes that reach p < 0.05 in a small trial, when the primary outcomes did not, are usually treated as hypotheses for future work.

Reviews of the Paediatric Evidence

Two more recent reviews focus on children and reach cautious conclusions.

The 2023 review of extract EA 575

EA 575 is a specific dry extract of ivy leaves (drug-to-extract ratio 5–7.5:1, made with 30% ethanol). A 2023 review combined a literature search with an online survey of ten international paediatric cough experts. It identified 10 controlled clinical trials and 9 observational studies. Controlled trials reported improvements in lung function and subjective cough symptoms; observational studies indicated favourable efficacy; the extract was generally well tolerated in children of all ages, including infants under one year. The survey experts broadly agreed and mentioned possible benefits on sleep. The conclusion: the extract "may provide clinical benefits in pediatric patients; however, more robust clinical trials are needed to confirm its efficacy" (Seifert 2023). The plain-language summary notes that the controlled studies "included only a small number of children".

The 2025 review of herbal medicines for children's respiratory infections

A systematically conducted review searched PubMed and the Cochrane Library for clinical studies of herbal medicines in children with acute respiratory tract infections. It included 45 reports, of which only nine were double-blind, placebo-controlled trials. Ivy leaf dry extract was among the single-herb products covered, and a thyme-plus-ivy combination among the fixed combinations. The review concluded that only Pelargonium sidoides extract EPs 7630 had sufficient evidence, and that for the other herbal products "further research is needed to close existing evidence gaps" (Kamin 2025). The review declares funding from a herbal-medicine manufacturer.

The overall paediatric picture

The 2026 evidence-map review summarises it: paediatric efficacy evidence "is dominated by observational studies and small airway function trials" (Pawłowska 2026).

Multi-Herb Products

Many cough products combine ivy with other herbs, and trials of these products test the mixture, not ivy. A 2019 comparative phase II trial in Pakistan, for example, tested chewable tablets made from marshmallow root (Althaea officinalis), ivy leaf and Sisymbrium irio seed against another multi-herb product in 70 patients over 15 days, using a cough quality-of-life questionnaire. The test group scored higher, and no side effects were reported (Khan 2019). Any benefit cannot be assigned to one ingredient, there was no placebo, and the analysis used before-and-after comparisons within groups.

The Korean phase 3 trial described above is another example: its new product combined ivy with Coptis. The narrative review of ivy in respiratory problems notes that ivy comes in many formulations, including tablets, liquids and topical ointments (Baharara 2021); comparing results across these products is difficult because the extracts, doses and partner herbs all differ.

What the Evidence Adds Up To

• In adults with acute cough: a handful of randomised trials show a faster fall in cough scores; an independent review judges the effect minimal and the evidence at high risk of bias. The 2026 review reads the placebo-controlled adult trials of one extract as showing greater short-term improvement than placebo (Pawłowska 2026).
• In children with acute cough: mostly observational data. Large open studies report high improvement rates and low side-effect rates but cannot show the extract caused the improvement.
• In children with asthma: one small placebo-controlled trial positive on airway resistance; one placebo-controlled crossover trial negative on its primary outcomes.
• Tolerability: consistently good over short courses, with gastrointestinal upset the most common complaint.
• Missing: large, independently funded, placebo-controlled trials with outcomes that matter to patients, such as days to recovery, sleep, and time off school or work.

Put plainly, the research shows a well-tolerated medicine with a small, uncertain effect on cough, studied far more often than it has been studied well. The safety side, including the European contraindication in children under two, is covered on the safety in children and allergy page.

Key Research Papers

1. Sierocinski E, Holzinger F, Chenot JF. Ivy leaf (Hedera helix) for acute upper respiratory tract infections: an updated systematic review. European journal of clinical pharmacology. 2021;77(8):1113-1122. PubMed PMID: 33523253
2. Fazio S, Pouso J, Dolinsky D, et al. Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicentre postmarketing study in 9657 patients. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2009;16(1):17-24. PubMed PMID: 16860549
3. Cho YJ, Yoon HJ, Lim DH, et al. Randomized, Double-Blind, Multicenter, Phase 3 Study of AG NPP709 Compared With Ivy Leaf Extract in Patients With Acute or Chronic Respiratory Symptoms. Journal of Korean medical science. 2026;41(9):e97. PubMed PMID: 41807028
4. Hofmann D, Hecker M, Völp A. Efficacy of dry extract of ivy leaves in children with bronchial asthma--a review of randomized controlled trials. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2003;10(2-3):213-20. PubMed PMID: 12725580
5. Zeil S, Schwanebeck U, Vogelberg C. Tolerance and effect of an add-on treatment with a cough medicine containing ivy leaves dry extract on lung function in children with bronchial asthma. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2014;21(10):1216-20. PubMed PMID: 24916707
6. Seifert G, Upstone L, Watling CP, et al. Ivy leaf dry extract EA 575 for the treatment of acute and chronic cough in pediatric patients: review and expert survey. Current medical research and opinion. 2023;39(10):1407-1417. PubMed PMID: 37731370
7. Kamin W, Seifert G, Zwiauer K, et al. Phytotherapy for acute respiratory tract infections in children: a systematically conducted, comprehensive review. Frontiers in pediatrics. 2025;13:1423250. PubMed PMID: 40376625
8. Pawłowska AM. From Traditional Remedy to Evidence-Based Phytotherapeutic Agent: Hedera helix L. in Respiratory Medicine. Plants (Basel, Switzerland). 2026;15(17). PubMed PMID: 42739377
9. Khan M, Rehman H, Naveed S, et al. Chewable cough tablets with improved palatability: A comparative phase II clinical trial. Pakistan journal of pharmaceutical sciences. 2019;32(1(Supplementary)):339-343. PubMed PMID: 30829213
10. Baharara H, Moghadam AT, Sahebkar A, et al. The Effects of Ivy (Hedera helix) on Respiratory Problems and Cough in Humans: A Review. Advances in experimental medicine and biology. 2021;1328:361-376. PubMed PMID: 34981489

PubMed Topic Searches

1. PubMed: ivy leaf extract cough randomized
2. PubMed: Hedera helix children cough
3. PubMed: Hedera helix asthma

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Connections

• Respiratory and Lung Herbs — the category hub
• Ivy Leaf (Hedera helix) — the main topic page
• Ivy Leaf: Benefits Deep Dive — the evidence ledger
• Alpha-Hederin and the Beta2 Mechanism — the proposed mechanism
• Safety in Children and Allergy — side effects and regulatory limits
• Ivy Leaf vs Thyme and Other Cough Herbs — the comparisons
• Thyme — ivy's most common partner herb
• Marshmallow Root — in the chewable-tablet combination
• Bronchitis — the condition most trials studied
• Asthma — the paediatric lung-function trials
• Common Cold — the usual start of an acute cough
• Chronic Cough — when a cough does not settle
• Honey: Cough Suppressant Evidence — another studied cough remedy

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